CN107349426B - Aspirin is combined with Herceptin or cooperates with the application in oncotherapy - Google Patents
Aspirin is combined with Herceptin or cooperates with the application in oncotherapy Download PDFInfo
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- CN107349426B CN107349426B CN201710568096.5A CN201710568096A CN107349426B CN 107349426 B CN107349426 B CN 107349426B CN 201710568096 A CN201710568096 A CN 201710568096A CN 107349426 B CN107349426 B CN 107349426B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
Abstract
Combine the invention discloses aspirin with Herceptin or cooperate with the application in oncotherapy, be related to oncotherapy technical field.Relative to individually applying Herceptin, by aspirin and Herceptin drug combination, HER2 positive tumor cells propagation can significantly be suppressed and promote the apoptosis of HER2 positive tumor cells, the effect of aspirin and the anti-HER2 positive tumors of Herceptin drug combination, which is better than, individually applies Herceptin.Present invention firstly discovers that the new application of aspirin, the effect of it helps to increase Herceptin.Aspirin provided by the invention, which is combined or cooperateed with Herceptin, is preparing the application in being used to treat the medicine of tumour, it is not only that aspirin provides theoretical foundation in the anticarcinogenic effect of HER2 positive tumors, while also the treatment for tumour especially HER2 positive tumors such as HER2 positive breast cancers or HER2 positive gastric carcinomas provides a kind of new thinking and treatment means.
Description
Technical field
The present invention relates to oncotherapy technical field, combines or assists with Herceptin in particular to aspirin
With the application in oncotherapy.
Background technology
At present, malignant tumour has become the principal disease for threatening human health.Human epidermal growth factor receptor 2 (Human
Epidermal Growth Factor Receptor-2, Her-2) positive malignant tumour wellability is strong, patient's disease-free survival
Phase is short, poor prognosis.
HER2 positive breast cancers account for the 20%~30% of whole breast cancer, in all molecule partings of breast cancer, HER2
Positive early-stage breast cancer it is shorter to DISTANT METASTASES IN time and total life span.The HER2 positives are stomach cancer common molecules point
Type, the stomach cancer that there are about 20% according to statistics are in HER2 positive, and the parting is high compared with other stomach cancer parting grade malignancies.Therefore, for
The treatment and research of HER2 positive malignancies enjoy researcher to pay close attention to.Herceptin (Trastuzumab, Herceptin) is a kind of
Monoclonal antibody is fitted together to for people/mouse of HER2 Oncoproteins, can specifically act on the cancer cell of HER2 acceptors overexpression simultaneously
And play lethal effect.Although Herceptin can effectively improve the effect of HER2 positive breast cancers, stomach cancer, regrettable
, only about 30% HER2 positive breast cancers, patients with gastric cancer positive effect, and most of initially receive Herceptin and control
Treat effective patient and often produced resistance in 1 year, plus its high cost, this clinic that significantly limit Herceptin should
With.Therefore, find for the new Therapeutic mode of HER2 positive malignancies, the effect of increasing Herceptin, have important
Clinical meaning.
In consideration of it, special propose the present invention.
The content of the invention
Combine it is an object of the invention to provide aspirin with Herceptin and preparing the medicine for treating tumour
In application.
Another object of the present invention is to provide aspirin and cooperate with Herceptin to be used to treat tumour in preparation
Application in medicine.
Combine or cooperate with another object of the present invention is to providing aspirin and Herceptin and preparing for suppressing
Application in the inhibitor of tumor cell proliferation.
Combine or cooperate with another object of the present invention is to providing aspirin and Herceptin and preparing for promoting
Application in the accelerator of apoptosis of tumor cells.
Another object of the present invention is to provide a kind of drug regimen for being used to treat tumour.
Another object of the present invention is to provide a kind of method for treating tumour.
What the present invention was realized in：
Aspirin is combined with Herceptin is preparing the application in being used to treat the medicine of tumour.
Aspirin cooperates with Herceptin is preparing the application in being used to treat the medicine of tumour.
Aspirin, which is combined or cooperateed with Herceptin, to be prepared for suppressing in the inhibitor of tumor cell proliferation
Using.
Aspirin, which is combined or cooperateed with Herceptin, to be prepared for promoting in the accelerator of apoptosis of tumor cells
Using.
A kind of drug regimen for being used to treat tumour, it includes Herceptin, and for joining with the Herceptin
Close or cooperate with the aspirin applied.
A kind of method for treating tumour, it includes：Herceptin is applied to the patient with tumour, and combines or cooperates with
Using aspirin.
The invention has the advantages that：
The effect of research of the present invention is found that the new application of aspirin first, and it helps to increase Herceptin,
I.e. relative to Herceptin is individually applied, by aspirin and Herceptin drug combination, it can significantly suppress HER2
The apoptosis of HER2 positive tumor cells, the effect of the anti-HER2 positive tumors of drug combination are bred and promoted to positive tumor cell
It is better than the effect for individually applying Herceptin.Therefore, aspirin provided by the invention is combined or assisted with Herceptin
With the application in being used to treat the medicine of tumour is being prepared, only aspirin is not in the anti-of tumour especially HER2 positive tumors
Cancer effect provides certain theoretical foundation, at the same also for tumour especially HER2 positive tumors (such as HER2 positive breast cancers or
HER2 positive gastric carcinomas) treatment provide a kind of new thinking and treatment means.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below by embodiment it is required use it is attached
Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore be not construed as pair
The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this
A little accompanying drawings obtain other related accompanying drawings.
Fig. 1 is that the aspirin combination Herceptin that the embodiment of the present invention 2 provides increases to HER2 positive breast cancer cells
The influence result grown；
Fig. 2 is that the aspirin combination Herceptin that the embodiment of the present invention 2 provides is bred to HER2 positive gastric carcinomas cell
Influence result；
Fig. 3 is that the aspirin combination Herceptin that the embodiment of the present invention 3 provides withers to HER2 positive breast cancer cells
The influence result died；
Fig. 4 is shadow of the aspirin combination Herceptin to HER2 positive gastric carcinoma Apoptosis of the embodiment of the present invention 3
Ring result.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer
Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment
The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, it is the conventional production that can be obtained by commercially available purchase
Product.
The aspirin of the embodiment of the present invention is combined with Herceptin or cooperates with the application in oncotherapy below
It is specifically described.
Aspirin has been applied to clinically a century, it is with outstanding anti-freezing and the protection heart as a kind of analgesic-antipyretic
Dirty effect turns into the line of angiocardiopathy one and Primary Care medication.
Antitumaous effect about aspirin in terms of tumour is also imperfectly understood.For aspirin and Herceptin
It is even more not have to combine for the report of HER2 positive tumors research.
The research of the present invention is found first, relative to Herceptin is individually applied, by aspirin and toltrazuril list
Anti- drug combination, it can significantly suppress HER2 positive tumors (such as HER2 positive breast cancers or HER2 positive gastric carcinomas) cell propagation
And promote the apoptosis of HER2 positive tumors (such as HER2 positive breast cancers or HER2 positive gastric carcinomas) cell, aspirin and song
The anti-HER2 positive tumors such as effect of HER2 positive breast cancers or HER2 positive gastric carcinomas of trastuzumab drug combination is better than list
Solely apply the effect of Herceptin or aspirin.Present invention firstly discovers that the new application of aspirin, by itself and song
The effect of trastuzumab is used in combination, and aspirin helps to increase Herceptin.
Based on this, on the one hand, combine the invention provides aspirin with Herceptin and preparing for treating tumour
Medicine in application.
Further, in some embodiments of the present invention, above-mentioned tumour is HER2 positive tumors.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumors be HER2 positive breast cancers or
HER2 positive gastric carcinomas.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
On the other hand, cooperateed with the invention provides aspirin with Herceptin and preparing the medicine for treating tumour
In application.
Further, in some embodiments of the present invention, above-mentioned tumour is HER2 positive tumors.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumors be HER2 positive breast cancers or
HER2 positive gastric carcinomas.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
On the other hand, combine the invention provides aspirin with Herceptin or cooperate with and preparing for suppressing tumour
Application in the inhibitor of cell propagation.
Further, in some embodiments of the present invention, above-mentioned tumour cell is HER2 positive tumor cells.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumor cells are HER2 positive breasts
Cancer cell or HER2 positive gastric carcinoma cells.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
On the other hand, combine the invention provides aspirin with Herceptin or cooperate with and preparing for promoting tumour
Application in the accelerator of Apoptosis.
Further, in some embodiments of the present invention, above-mentioned tumour cell is HER2 positive tumor cells.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumor cells are HER2 positive breasts
Cancer cell or HER2 positive gastric carcinoma cells.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
On the other hand, the invention provides a kind of drug regimen for being used to treat tumour, it includes Herceptin, and
For combining or cooperateing with the aspirin applied with above-mentioned Herceptin.
Further, in some embodiments of the present invention, above-mentioned tumour is HER2 positive tumors.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumors be HER2 positive breast cancers or
HER2 positive gastric carcinomas.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
On the other hand, the invention provides a kind of method for treating tumour, it includes：Applied to the patient with tumour bent
Trastuzumab, and combine or cooperate with and apply aspirin.
Further, in some embodiments of the present invention, above-mentioned tumour is HER2 positive tumors.
Further, in some embodiments of the present invention, above-mentioned HER2 positive tumors be HER2 positive breast cancers or
HER2 positive gastric carcinomas.
Further, in some embodiments of the present invention, the mass ratio of aspirin and Herceptin is 60：
(1-2)。
Aspirin provided by the invention, which is combined or cooperateed with Herceptin, to be prepared for treating in the medicine of tumour
Application, only aspirin does not provide certain theoretical foundation in the anticarcinogenic effect of tumour especially HER2 positive tumors, together
When treatment also for tumour especially HER2 positive tumors (such as HER2 positive breast cancers or HER2 positive gastric carcinomas) provide one
Kind new thinking and treatment means.
The feature and performance of the present invention are described in further detail with reference to embodiments.
Cell line and main agents
HER2 positive breast cancer cell lines SKBR3, HER2 positive gastric carcinoma cell lines SGC7901 is derived from Chinese Academy of Sciences Shanghai
Cell bank, preserved by Lanzhou hospital general of Chinese People's Liberation Army experimental center.SKBR3 cells and SGC7901 cells use
DMEM nutrient solutions (containing 10% hyclone) are in 37 DEG C, 5%CO2Cultivated in incubator.Aspirin (Acetylsalicylic
Acid), MTT (3- (4,5- dimethylthiazoles -2) -2,5- diphenyltetrazolium bromide bromides) is purchased from Sigma companies.Injection is bent
Trastuzumab is purchased from Roche Holding Ag.Aspirin is dissolved in dimethyl sulfoxide (DMSO) (DMSO), and Herceptin is dissolved in sterile water for injection.
Embodiment 1
A kind of drug regimen for being used to treat tumour is present embodiments provided, the drug regimen includes Herceptin, with
And for combining or cooperateing with the aspirin applied with Herceptin.
The drug regimen that the present embodiment provides to tumour especially HER2 positive tumors such as HER2 positive breast cancers or
HER2 positive gastric carcinomas have preferable therapeutic effect.
Embodiment 2
The influence that 1 aspirin combination Herceptin is bred to HER2 positive breast cancer cells SKBR3
Mtt assay detection cell propagation
96 porocyte culture plates will be inoculated in after the SKBR3 passages of normal growth, per the μ l volumes of hole 200, cell number
For 2 × 103It is individual, it is separately added into after overnight incubation containing 5mM aspirin (5mM Aspirin), 15 μ g/ml Herceptins
(15 μ g/ml Trastuzumab), 30 μ g/ml Herceptins (30 μ g/ml Trastuzumab) and two medicines joint (5mM
Aspirin+15 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are 60:1)、(5mM
Aspirin+30 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are 60:2) nutrient solution continues
Culture, to add the nutrient solution of isometric water for injection or DMSO (i.e. control groups) as a control group, detects cell after 2d
Proliferative conditions.It is 5mg/ml by MTT configuration concentrations, continues to cultivate 4h after 20 μ l are added per hole, abandon nutrient solution afterwards, added per hole
150 μ l DMSO, about 5min is vibrated on ELIASA, 490nm detection absorbance (OD) values, draws histogram graph representation cell growth
Situation, as a result as shown in Figure 1 (in figure：Ordinate represents cell proliferation rate, and abscissa represents different medication groups).Every group 3 multiple
Hole, and be repeated 3 times, as a result represented with (mean+SD).
Fig. 1 result shows that control groups cell is that (100 ± 6.13) %, 5mM aspirin groups are thin with respect to proliferation rate
Born of the same parents are (79.6 ± 4.51) % with respect to proliferation rate, 15 μ g/ml Herceptin group cells with respect to proliferation rate for (69.2 ±
2.23) %, 30 μ g/ml Herceptin group cells are (48.2 ± 5.80) %, 5mM Aspirin+15 μ g/ml with respect to proliferation rate
Trastuzumab groups cell is (46.1 ± 7.01) %, 5mM Aspirin+30 μ g/ml Trastuzumab groups with respect to proliferation rate
Cell is (21.5 ± 2.89) % with respect to proliferation rate.Statistical analysis is shown, compared with control groups, 5mM aspirin group, 15 μ
The cell propagation of g/ml Herceptins group, 30 μ g/ml Herceptins groups and two medicine joint groups is suppressed, and difference has system
Meter learns meaning (P<0.05)；No matter with 5mM aspirin group, 15 μ g/ml Herceptins groups, 30 μ g/ml Herceptin groups
Compare, the cell propagation of two medicine joint groups is substantially suppressed, and difference has statistical significance (P<0.05), and two differences are dense
The proliferation rate of two medicine joint groups of degree is less than single medicine group.Thus illustrate, aspirin combination Herceptin can substantially suppress
SKBR3 cells breed, and inhibition be better than be used alone Herceptin situation, aspirin can promote or increase or
Amplification cooperates with inhibitory action of the Herceptin to HER2 positive breast cancer cells.
The influence that 2 aspirin combination Herceptins are bred to HER2 positive gastric carcinoma cells SGC7901
Mtt assay detection cell propagation
96 porocyte culture plates will be inoculated in after the SGC7901 passages of normal growth, per the μ l volumes of hole 200, cell
Number is 2 × 103It is individual, it is separately added into after overnight incubation containing 5mM aspirin (5mM Aspirin), 15 μ g/ml Herceptins
(15 μ g/ml Trastuzumab), 30 μ g/ml Herceptins (30 μ g/ml Trastuzumab) and two medicines joint (5mM
Aspirin+15 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are 60:1)、(5mM
Aspirin+30 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are 60:2) nutrient solution continues
Culture, to add the nutrient solution of isometric water for injection or DMSO (i.e. control groups) as a control group, detects cell after 2d
Proliferative conditions.It is 5mg/ml by MTT configuration concentrations, continues to cultivate 4h after 20 μ l are added per hole, abandon nutrient solution afterwards, added per hole
150 μ l DMSO, about 5min is vibrated on ELIASA, 490nm detection absorbance (OD) values, draws histogram graph representation cell growth
Situation, as a result as shown in Figure 2 (in figure：Ordinate represents cell proliferation rate, and abscissa represents different medication groups).Every group 3 multiple
Hole, and be repeated 3 times, as a result represented with (mean+SD).
Fig. 2 result shows that control groups cell is that (100 ± 1.72) %, 5mM aspirin groups are thin with respect to proliferation rate
Born of the same parents are (80.3 ± 5.66) % with respect to proliferation rate, 15 μ g/ml Herceptin group cells with respect to proliferation rate for (76.0 ±
3.11) %, 30 μ g/ml Herceptin group cells are (57.3 ± 3.54) %, 5mM Aspirin+15 μ g/ml with respect to proliferation rate
Trastuzumab groups cell is (47.5 ± 6.20) %, 5mM Aspirin+30 μ g/ml Trastuzumab groups with respect to proliferation rate
Cell is (26.5 ± 1.66) % with respect to proliferation rate.Statistical analysis is shown, compared with control groups, 5mM aspirin group, 15 μ
The cell propagation of g/ml Herceptins group, 30 μ g/ml Herceptins groups and two medicine joint groups is suppressed, and difference has system
Meter learns meaning (P<0.05)；No matter with 5mM aspirin group, 15 μ g/ml Herceptins groups, 30 μ g/ml Herceptin groups
Compare, the cell propagation of two medicine joint groups is substantially suppressed, and difference has statistical significance (P<0.05).As can be seen here, phase
Compared with the situation that Herceptin is used alone, it is used in combination in aspirin and Herceptin SGC7901 cells are increased
The inhibition grown is more preferable, and aspirin can promote or increase or amplify or cooperate with Herceptin thin to HER2 positive gastric carcinomas
The inhibitory action of born of the same parents.
Embodiment 3
Influence of the aspirin combination Herceptin to HER2 positive breast cancer cells SKBR3 Apoptosis
Flow cytometry detects Apoptosis
It will be inoculated in after the SKBR3 passages of normal growth in culture dish, treat that cell density reached for 80% or so time-division
Jia Ru contain 5mM aspirin (5mM Aspirin), 30 μ g/ml Herceptins (30 μ g/ml Trastuzumab) and
(5mM Aspirin+30 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are 60 to two medicines joint:
2) nutrient solution continues to cultivate, to add the nutrient solution of isometric water for injection or DMSO (i.e. control groups) as a control group,
Cell is post-processed in 72h.It will be resuspended after cell dissociation, adjustment cell number is 1 × 106Individual/ml, added after being washed 2-3 times with PBS
500 μ l buffer solution suspension cells, then be separately added into 10 μ l annexin V- fluorescein isothiocynates (Annexin V-FITC) and
10 μ l PI are mixed, and room temperature lucifuge is incubated dyeing 15min, and flow cytometer carries out Two Colour Fluorescence cell cytometry.As a result such as
Shown in Fig. 3 (in figure：A is FCM analysis of the aspirin combination Herceptin to HER2 positive breast cancer cells apoptosis
As a result；B is that department woods combines influence result block diagram of the Herceptin to HER2 positive breast cancer cells apoptosis, is schemed in B：It is vertical
Coordinate is apoptosis rate, and abscissa is different medication group).
Fig. 3 result shows that control groups apoptosis rate is that (13.5 ± 3.20) %, 5mM aspirin group cells wither
It is (27.3 ± 3.47) % to die rate, and 30 μ g/ml Herceptin groups apoptosis rates are (35.3 ± 2.80) %, 5mM
Aspirin+30 μ g/ml Trastuzumab groups apoptosis rate is (56.2 ± 3.95) %.Statistical analysis shows, with
Control groups are compared, the Apoptosis increase of 5mM aspirin group, 30 μ g/ml Herceptins groups and two medicine joint groups, poor
It is different that there is statistical significance (P<0.05)；Though compared with 5mM aspirin group or 30 μ g/ml Herceptin groups, two medicines connection
Charge-coupled Apoptosis substantially increases, and difference has statistical significance (P<0.05).Thus illustrate, it is bent appropriate compared to being used alone
The situation of pearl monoclonal antibody, it is more preferable that aspirin and Herceptin are used in combination its facilitation effect to SKBR3 Apoptosis, this
Show, aspirin can strengthen or promote or amplify or cooperate with Herceptin to promote apoptosis to HER2 positive breast cancer cells
Effect.
Embodiment 4
Influence of the aspirin combination Herceptin to HER2 positive gastric carcinoma cell SGC7901 Apoptosis
Flow cytometry detects Apoptosis
It will be inoculated in after the SGC7901 passages of normal growth in culture dish, when cell density reaches 80% or so
Be separately added into containing 5mM aspirin (5mM Aspirin), 30 μ g/ml Herceptins (30 μ g/ml Trastuzumab) with
And two medicine joint (5mM Aspirin+30 μ g/ml Trastuzumab, the i.e. mass ratio of aspirin and Herceptin are
60:2) nutrient solution continues to cultivate, to add the nutrient solution of isometric water for injection or DMSO (i.e. control as a control group
Group), post-process cell in 72h.It will be resuspended after cell dissociation, adjustment cell number is 1 × 106Individual/ml, add after being washed 2-3 times with PBS
Enter 500 μ l buffer solution suspension cells, then be separately added into 10 μ l annexin V- fluorescein isothiocynates (Annexin V-FITC)
Mixed with 10 μ l PI, room temperature lucifuge is incubated dyeing 15min, and flow cytometer carries out Two Colour Fluorescence cell cytometry.As a result
As shown in Figure 4 (in figure：A is FCM analysis of the aspirin combination Herceptin to HER2 positive gastric carcinoma Apoptosis
As a result；B is that department woods combines influence result block diagram of the Herceptin to HER2 positive gastric carcinoma Apoptosis, is schemed in B：It is vertical to sit
Apoptosis rate is designated as, abscissa is different medication group).
Fig. 4 result shows that control groups apoptosis rate is that (11.8 ± 1.22) %, 5mM aspirin group cells wither
It is (28.7 ± 1.53) % to die rate, and 30 μ g/ml Herceptin groups apoptosis rates are (32.0 ± 2.22) %, 5mM
Aspirin+30 μ g/ml Trastuzumab groups apoptosis rate is (71.5 ± 2.54) %.Statistical analysis shows, with
Control groups are compared, the Apoptosis increase of 5mM aspirin group, 30 μ g/ml Herceptins groups and two medicine joint groups, poor
It is different that there is statistical significance (P<0.05)；Though compared with 5mM aspirin group or 30 μ g/ml Herceptin groups, two medicines connection
Charge-coupled Apoptosis substantially increases, and difference has statistical significance (P<0.05).Thus illustrate, it is bent appropriate compared to being used alone
The situation of pearl monoclonal antibody, it is more preferable that aspirin and Herceptin are used in combination its facilitation effect to SGC7901 Apoptosis,
This shows that aspirin can strengthen or promote or amplify or cooperate with Herceptin to promote apoptosis to HER2 positive gastric carcinomas cell
Effect.
These results suggest that, aspirin can strengthen or promote or amplify or cooperate with Herceptin to tumour especially
The Inhibit proliferaton of HER2 positive tumors or the effect for promoting apoptosis, this discovery is unexpected, allows those skilled in the art to be taken aback.
Embodiment 4
A kind of method for treating tumour is present embodiments provided, it includes：Toltrazuril list is applied to the patient with tumour
It is anti-, and combine or cooperate with and apply aspirin.
The method for the treatment tumour that the present embodiment provides is to tumour especially HER2 positive tumors (such as HER2 positive breasts
Cancer or HER2 positive gastric carcinomas) there is preferable therapeutic effect.
Aspirin is used usually as a kind of non-antineoplastic, but the present invention studies have shown that its can put
The effect of big or collaboration or enhancing traditional anti-tumor medicine (such as Herceptin), find first and confirm aspirin
New application, the result is astonishing, beyond the expectation of those skilled in the art.Therefore, aspirin can be with Herceptin
Combine or cooperate with for preparing treatment tumour especially HER2 positive tumors (such as HER2 positive breast cancers or HER2 positive stomaches
Cancer) medicine in.Aspirin and Herceptin are used in combination, it is positive to be used for HER2 as a kind of brand-new Therapeutic mode
The treatment of tumour possesses following advantage：
First, this new model adds the effect of Herceptin is used alone.
For example, be used alone Herceptin HER2 positive breast cancer cells proliferation rate be only (48.2 ±
5.80) %, after Herceptin joint aspirin use, the proliferation rates of HER2 positive breast cancer cells be reduced to (21.5 ±
2.89) %, ratio is reduced up to 55.4%；Herceptin is used alone is only to the apoptosis rate of HER2 positive breast cancer cells
(35.3 ± 2.80) %, Herceptin joint aspirin reach (56.2 ± 3.95) % using rear apoptosis rate, increased
Ratio is up to 58.9%.This be used in combination has obtained similar result in HER2 positive gastric carcinoma cells.Thus Herceptin
The use of joint aspirin to HER2 positive breast cancers, stomach cancer cell Inhibit proliferaton, promote apoptotic effect clearly, this effect
Fruit is that those skilled in the art can not expect to obtain.
Secondly, this new model can reduce the toxicity of patient.
It can not only increase the treatment of traditional anti-tumor medicine using aspirin is combined as a kind of antineoplaston new model
Effect, it is often more important that reduce Chemotherapy in Patients toxicity.This Therapeutic mode is different from the letter of clinically two kinds of antineoplastics
Simply connected closes, because aspirin is not antineoplastic, therefore toxicity also violent without antineoplastic.It is this new
Pattern can reduce the toxicity of patient, mitigate the pain of patient, avoid doctor-patient dispute, realize people-oriented treatment mesh
's.
Further, this new model can reduce medical treatment cost, save medical resources.
Herceptin has high expenses for medicine, and 1 patient is using the total cost of Herceptin 150,000 or so.But
It is for some patientss, to be treated even if having paid expense and having employed this mode, there is also Herceptin reactivity is poor
The problem of, it is impossible to the therapeutic effect reached.Aspirin is low-cost, is readily available, and aspirin is bent appropriate in increase
Extra expenses for medicine is not increased again while the effect of pearl monoclonal antibody.The research of the present invention alleviates for HER2 positive tumor patients to be controlled
Treatment expense is born, and saves social medical resource.
In a word, research of the invention shows, aspirin is combined with Herceptin or cooperateed with swollen available for treatment is prepared
In knurl especially HER2 positive tumors such as HER2 positive breast cancers or the medicine of HER2 positive gastric carcinomas, and aspirin and song
Trastuzumab is combined or collaboration can be used for the inhibitor for preparing suppression tumor cell proliferation or the promotion for promoting apoptosis of tumor cells
In agent.This is not only that especially the anticarcinogenic effect of HER2 positive tumors provides certain theoretical foundation to aspirin in terms of tumour,
Also provide one for the treatment to tumour especially HER2 positive tumors such as HER2 positive breast cancers or HER2 positive gastric carcinomas simultaneously
Kind new thinking and treatment means.
The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention, for the skill of this area
For art personnel, the present invention can have various modifications and variations.Within the spirit and principles of the invention, that is made any repaiies
Change, equivalent substitution, improvement etc., should be included in the scope of the protection.
Claims (4)
1. aspirin is combined with Herceptin is preparing the application in being used to treat the medicine of tumour, it is characterised in that institute
It is HER2 positive tumors to state tumour, and the HER2 positive tumors are HER2 positive breast cancers or HER2 positive gastric carcinomas, aspirin
Mass ratio with Herceptin is 60：(1-2).
2. aspirin is combined with Herceptin is preparing the application in being used to suppress the inhibitor of tumor cell proliferation, it is special
Sign is, the tumour is HER2 positive tumors, and the HER2 positive tumors are HER2 positive breast cancers or HER2 positive gastric carcinomas,
The mass ratio of aspirin and Herceptin is 60：(1-2).
3. aspirin is combined with Herceptin is preparing the application in being used to promote the accelerator of apoptosis of tumor cells, it is special
Sign is, the tumour is HER2 positive tumors, and the HER2 positive tumors are HER2 positive breast cancers or HER2 positive gastric carcinomas,
The mass ratio of aspirin and Herceptin is 60：(1-2).
4. a kind of be used to treat the drug regimen of tumour, it is characterised in that it includes Herceptin, and for the song
The aspirin that trastuzumab is administered in combination, the tumour are HER2 positive tumors, and the HER2 positive tumors are HER2 positive
The mass ratio of breast cancer or HER2 positive gastric carcinomas, aspirin and Herceptin is 60：(1-2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710568096.5A CN107349426B (en) | 2017-07-12 | 2017-07-12 | Aspirin is combined with Herceptin or cooperates with the application in oncotherapy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710568096.5A CN107349426B (en) | 2017-07-12 | 2017-07-12 | Aspirin is combined with Herceptin or cooperates with the application in oncotherapy |
Publications (2)
| Publication Number | Publication Date |
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| CN107349426A CN107349426A (en) | 2017-11-17 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1466464A (en) * | 2000-07-28 | 2004-01-07 | ס����ҩ��ʽ���� | Novel remedies for cancer |
| WO2015023703A1 (en) * | 2013-08-12 | 2015-02-19 | Pharmacyclics, Inc. | Methods for the treatment of her2 amplified cancer |
| CN104755497A (en) * | 2012-05-11 | 2015-07-01 | 梅里麦克制药股份有限公司 | Dosage and administration of bispecific SCFV conjugates in combination with anti-cancer therapeutics |
| CN106139151A (en) * | 2016-04-29 | 2016-11-23 | 陈西敬 | Ascorbic acid palmityl ester and the synergistic pharmaceutical composition of antitumor drug |
| WO2017007846A1 (en) * | 2015-07-07 | 2017-01-12 | Genentech, Inc. | Combination therapy with an anti-her2 antibody-drug conjugate and a bcl-2 inhibitor |
-
2017
- 2017-07-12 CN CN201710568096.5A patent/CN107349426B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1466464A (en) * | 2000-07-28 | 2004-01-07 | ס����ҩ��ʽ���� | Novel remedies for cancer |
| CN104755497A (en) * | 2012-05-11 | 2015-07-01 | 梅里麦克制药股份有限公司 | Dosage and administration of bispecific SCFV conjugates in combination with anti-cancer therapeutics |
| WO2015023703A1 (en) * | 2013-08-12 | 2015-02-19 | Pharmacyclics, Inc. | Methods for the treatment of her2 amplified cancer |
| WO2017007846A1 (en) * | 2015-07-07 | 2017-01-12 | Genentech, Inc. | Combination therapy with an anti-her2 antibody-drug conjugate and a bcl-2 inhibitor |
| CN106139151A (en) * | 2016-04-29 | 2016-11-23 | 陈西敬 | Ascorbic acid palmityl ester and the synergistic pharmaceutical composition of antitumor drug |
Non-Patent Citations (6)
| Title |
|---|
| Anthracycline cardiotoxicity in breast cancer patients: synergism with trastuzumab and taxanes;Luca Gianni等;《Cardiovasc Toxicol》;20070419;第7卷(第2期);第67-71页 * |
| Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study;Clarke CA等;《Breast Cancer Research》;20170501;第19卷(第1期);52 * |
| 曲妥珠单抗联合5-氟尿嘧啶和/或顺铂治疗胃癌的实验研究;李晓玲;《中国博士学位论文全文数据库 医药卫生科技辑》;20081115(第11期);E072-26 * |
| 细胞自噬促进拉帕替尼抗HER2阳性乳腺癌的机制研究;朱星枚;《中国博士学位论文全文数据库 医药卫生科技辑》;20140215(第2期);E079-21 第4-6页，第71页第2、3段，第77页第1段 * |
| 阿司匹林对HER-2阳性乳腺癌AU-565细胞增殖能力的影响;吴颖等;《中华乳腺病杂志（电子版）》;20170228;第11卷(第1期);第19-23页 * |
| 阿司匹林预防肿瘤的研究进展;蔡忠林 等;《现代肿瘤医学》;20170430;第25卷(第08期);第1329-1332页 * |
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