CN107648261A - A kind of medicine for treating cardia cancer and its application - Google Patents
A kind of medicine for treating cardia cancer and its application Download PDFInfo
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Abstract
The invention discloses a kind of medicine for treating cardia cancer and its application.Inventor is by studying for a long period of time, find that aluminum sulfate can differentiate identification human normal tissue and cancerous tissue first, change cancer cell physiological characteristic, suppress cancer cells secrete multiple proteins hydrolase, suppress the metabolic function of cancer cell mitochondria, so as to realize antitumor action, the medicine can be incorporated into the DNA of cancer cell, promote its cracking, quickly strong convergence it can condense cell surface glycoprotein, effectively change the protein structure of cell surface, disabling signal path, change Cell microstructure, and combined with succinate dehydrogenase in cell mitochondrial, effectively control cancer cell multiplication and transfer, 99.8~99.9% or even 100% are up to the inhibiting rate of cancer cell.Aluminum sulfate Small side effects, safe, oral medication cardia cancer has the advantages that dosage is micro-, rapid-action, short treating period, can reduce knurl body, apoptosis-induced, Inhibit proliferaton rapidly, final fragmentation comes off, and capturing cardia cancer to the mankind has important practical significance.
Description
Technical field
The present invention relates to a kind of new opplication of compound, more particularly to a kind of medicine for treating cardia cancer and its application.
Background technology
Cardia cancer is that the gland cancer under stomachus cardiacus, that is, gastric and esophageal boundary line about in the range of 2cm occurs.It is stomach cancer
Specific type, should be distinguished with Esophagogastrostomy fistula.But it is again different from the stomach cancer at other positions, has the anatomy group of oneself
Knit and learn characteristic and clinical manifestation.In China, the death rate and the incidence of disease of cardia cancer rank among the best in all kinds of malignant tumours.There is money
Material shows that the death rate of cardia cancer accounts for 12% of general mortality rate or so.
The cause of disease of cardia cancer
1st, nitrosamine compound is present in some foods, vegetables and drinking-water
2nd, the carcinogenesis of the mould food that goes mouldy can induce cardia cancer squamous carcinoma, may separate out from these foods geotrichum candidum,
Yellow mould, head mold and bud branch are mould etc. to induce animal tumor, and this kind of mould has the synergy for promoting cancer with nitrosamine.
3rd, molybdenum, copper, zinc, the content of nickel are relatively low in micro- people's vitro easily induces cardia cancer.
4th, the physics sexual stimulus of eating habit food such as heat, draw, be thick, hard, smoking, drink and nutritional deficiency all with it is beautifully adorned
The generation of door cancer is relevant.
5th, genetic predisposition.
6th, the canceration lesion oesophagus chronic inflammation of oesophagus, cardia achalasia card, sideropenic dysphagia all have with cardia cancer
Close.
Cardia cancer-immunization therapy zoopery and clinical trial are shown to be made by the following aspects to play cancer-resisting
With：
1st, the immunocyte such as activating phagocytic cells, constant killer cell, nocuity T cell, leukin, interference are induced
The secretion of the cell factors such as element-γ, tumor necrosis factor-alpha.
2nd, cancer cell specific induction of apoptosis.
3rd, shared with traditional chemotherapeutic agent (mitomycin, Ka Mosiding etc.), both increase drug effect, mitigate chemotherapy again
During toxic side effect.
4th, there is synergy with immunotherapy medicaments (interferon-' alpha ' 2b).
5th, slow down the pain of patient with advanced cancer, increase appetite, improve the quality of life of patient.
Existing Treatment for Cardiac Cancer high cost, side effect are big, and the life quality of patient is poor after treatment.Therefore, it is anxious at present
A kind of effectively treatment orifice of the stomach cancer drug is needed to solve the matter of great urgency of cancer patient.
Aluminum sulfate is a kind of common sulfate, the precipitating reagent in paper industry as sizing materials such as gum rosin, wax emulsions,
Make flocculant in water process, can also make the interior of foam annihilator and stay agent, the white raw material of manufacture alum, aluminium, oil decolourizes, deodorization
Agent, the auxiliary material etc. of some drugses.The the first big purposes of aluminum sulfate for constituting about total output 50% is to be used for papermaking, and second largest purposes is
Flocculant is made in drinking water, industrial water and Industrial Wastewater Treatment, constitutes about aluminum sulfate total output 40%.When into this kind of water
After adding aluminum sulfate, can generate glue, can adsorb and be settled out bacterium, the aluminium hydroxide of colloid and other suspensions wadding
Piece, the color and taste of water are can control in drinking water treatment.
In terms of medicine, aluminum sulfate also has a small amount of application, and such as all states are burned, and Wu Shurong, Chen Jinyun, wait compound aluminum sulfates
Prescription research [J] liberation medical academy journals of solution, 1981 (2) disclose intratumoral injection tumor of bladder achieve compared with
The effect of good, to the cure rate of early stage tumor of bladder up to 91.1%.Later stage is further investigations have shown that compound aluminum sulfate injection
There is certain therapeutic action to tumor of bladder, but subsequent 30 years for many years, have no that aluminum sulfate can be used for treating other
Tumour.
The content of the invention
It is an object of the invention to overcome the deficiencies of the prior art and provide a kind of medicine of better treatment cardia cancer
And its application.
The technical solution used in the present invention is：
A kind of medicine for treating cardia cancer, its active component include aluminum sulfate.
As the further improvement of said medicine, aluminum sulfate is aluminum sulfate more than food-grade, or pure with the following method
Change obtains：
1) by aluminum sulfate and ultra-pure water mixed dissolution, aluminum sulfate solution is obtained；
2) refined filtration is carried out to aluminum sulfate solution, freeze-drying obtains aluminum sulfate.
As the further improvement of said medicine, medicine is oral formulations.Further, oral formulations are selected from tablet, glue
Wafer, granule, liquid preparation.Particularly, preparation is oral tablet soluble in the stomach or gastric-dissolved capsule agent.
As the further improvement of said medicine, the mass mixing ratio of aluminum sulfate and ultra-pure water is 1：(2~5), after dissolving
The ultra-pure water purifying used.Further, the mass mixing ratio of aluminum sulfate and ultra-pure water is 1：3, the quality such as use after dissolving
Ultra-pure water purifies.
As the further improvement of said medicine, refined filtration is carried out to aluminum sulfate solution using the filter membrane that aperture is 0.22 μm.
As the further improvement of said medicine, aluminum sulfate is selected from the hydrate of aluminum sulfate.
The present invention captures after the research of many decades, and finds " aluminum sulfate " first, can differentiate identification human normal tissue
With cancerous tissue, its cancerous tissue is voluntarily come off from normal structure separation, while can differentiate and identify normal cell and cancer cell and select
Selecting property dies of hunger the breakthrough first of cancer cell.It is that the most fast most definite and low toxicity of the treatment curative effect to malignant tumour is efficient so far,
There is no inhibitory action substantially to normal cell, cancer cell can be killed rapidly and reduce knurl body generation primacy chemical drug, its curative effect is far excellent
Traditional anti-cancer medicine at present, its birth can save ten hundreds of patient vitals, and the malignant tumour that is particularly suitable for use in solid carcinoma is controlled
Treat.
Inventor is after many decades and puts into huge fund and is studied, and researches and develops world forefront primacy series anticancer of successfully having
Special efficacy new drug, its curative effect are treatment of the century-old mankind so far for malignant tumour solid carcinoma, chemicotherapy, operation and modern any controlled
What treatment means can not be realized, malignant tumour solid carcinoma can upon administration gradually voluntarily separated from human normal tissue and comes off.
Pharmacology：The critical path of Apoptosis is as follows：(1), cancer cell physiological characteristic can be changed.(2), cancer cells secrete is suppressed
Multiple proteins hydrolase.(3), the metabolic function of cancer cell mitochondria is suppressed, so as to realize antitumor action.(4), the medicine energy
It is attached in the DNA of cancer cell, promotes its cracking.(5), can quick strong convergence cohesion cell surface glycoprotein.(6), effectively control
Cancer cell multiplication and transfer.(7), the medicine can effectively change the protein structure of cell surface.(8), disabling signal path.(9), change
Become Cell microstructure.(10) and with succinate dehydrogenase in cell mitochondrial combined so as to change its biological effect.(11), because normal
Otherwise cell sucks regular this irregular characteristic of cancer cell.(12), the compound can identify differentiate normal structure with it is improper
Tissue, normal cell do not suppress normal cell with abnormal cell and selectively hungry to death and killing cancer cell so that malignant tumour
The physianthropy important breakthrough that fragment comes off gradually is presented in entity cancerous tissue, 99.8~99.9% is up to tumor control rate, very
To reaching 100%.
Toxicity：It is heavy dose of to have no obvious toxic-side effects through many decades research and test.
Drug effect：There are micro- dosage, rapid-action, short treating period, Small side effects, treating above-mentioned malignant tumour can contract rapidly
Tubercle body, apoptosis-induced, Inhibit proliferaton.
Usage and dosage：Oral maximum dosage：500mg/ grains, 4~6 every time, take day four times.One month course for the treatment of, 3
~5 courses for the treatment of are until recovery from illness, long-term use have no apparent side effect.
Function is with curing mainly：Cure mainly cardia cancer.
Cell experiment as shown by data aluminum sulfate has obvious suppression to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC propagation
Make and use, its IC50Respectively 8.393mg/ml；There is obvious apoptosis-promoting effect to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC, and
With concentration-effect relation；Can be by MFC cell-cycle arrests in G0/G1Phase, and there is concentration-effect relation.
By oral aluminum sulfate preparation for treating cardia cancer, there are micro- dosage, rapid-action, short treating period, Small side effects,
Knurl body, apoptosis-induced, Inhibit proliferaton can be reduced rapidly, and capturing cardia cancer to the mankind has important practical significance.
Brief description of the drawings
Fig. 1 is the HPLC chromatogram of aluminum sulfate after purification；
Fig. 2 is the pets of acute toxicity testing；
Fig. 3 is concentration-inhibiting rate curve of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC；
Fig. 4 is the influence that aluminum sulfate is bred to Mouse Stomach squamous cell carcinoma (orifice of the stomach position), and arrow represents non-viable non-apoptotic cell；
Fig. 5 is influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC apoptosis；In figure, A is Vehicle controls
Group, B are aluminum sulfate 10mg/ml groups, and C is aluminum sulfate 30mg/ml groups, and D is aluminum sulfate 100mg/ml groups；
Fig. 6 is influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC apoptosis, and arrow represents nucleus wrinkle
Contracting, prompts for apoptotic cell；
Fig. 7 is influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) the MFC apoptosis cycles；In figure, A is solvent pair
According to group, B is aluminum sulfate 10mg/ml groups, and C is aluminum sulfate 30mg/ml groups, and D is aluminum sulfate 100mg/ml groups.
Embodiment
Confirm the testing data of chemical constitution
Experiment commission Hunan Province's Experimental Animal Center (Drug Safety Evaluation Center of Hunan Province's progress).
First, new drug title, molecular formula and molecular weight
Chinese name：Aluminum sulfate
Molecular formula：Al2(SO4)3·18H2O, molecular weight：666.4.
2nd, the method for confirming chemical constitution
1st, determination of moisture
1.1 test condition：
Instrument：V-30 cassette moisture tellers
Method：《Chinese Pharmacopoeia》The first method of aquametry of four general rules of version in 2015 0832.
1.2 measurement result
Moisture measurement result in table 1, aluminum sulfate
1.3rd, parse
Calculated according to sulfuric acid constructed of aluminium and moisture, the number containing the crystallization water is 18 in structure.
The measure of aluminium element
2.1st, test condition
Instrument：Agilent 240-DUO original absorption spectrometers
Method：Using graphite oven atomic absorption, aluminium element content in aluminum sulfate sample is determined.
2.2nd, test result
Aluminium element test result in table 2, aluminum sulfate sample
As a result show：The mean percent content of aluminium element is 8.15% in aluminum sulfate sample.
2.3rd, parse
According to above-mentioned determination of moisture, calculated by 18 crystallizations water, the ratio that aluminium element accounts for molecular weight is 8.11%, and above-mentioned
The aluminium element content of atomic absorption detecting is consistent, further demonstrates that and contains aluminium element and 18 crystallizations water in sample.
The measure of sulfate ion
3.1st, test condition
Instrument：ICS900 ion chromatographs
Method：Using 25mM sodium hydroxides as leacheate, chromatographic column is Dionex IonpacTM As18 (4 × 250mm),
Flow velocity is 1.0ml/min, sample size 25ul；Using anhydrous sodium sulfate as reference substance, calculated and contained with external standard method by peak area
Amount.
3.2nd, test result
Sulfate radical content measurement result in table 3, aluminum sulfate
* it is actual concentrations.
After measured, it is 45.5% containing sulfate ion in sample.
3.3rd, parse
Sample chromatogram figure is consistent with reference substance chromatogram retention time, shows the sulfate radical containing high concentration in sample；Root
According to moisture and aluminium element assay result, ion-chromatographic determination sulfate ion content is used as 43.4%, with molecule knot
Sulfate ion molecular weight accounting is 43.2% basically identical in structure.
4th, conclusion
According to determination of moisture, aluminium element assay, sulfate radical content measurement result comprehensive analysis, this product molecular formula is
Al2(SO4)3·18H2O。
, can be directly using the high-purity sulphuric acid aluminium (analysis of manufacturer production in order to thoroughly prevent three-waste free discharge to avoid purifying
Pure or pharmaceutical grade), but have to carry out strict quality control from manufacturer source.
The purifying of aluminum sulfate
1) aluminum sulfate is pressed 1:3 mass ratio is dissolved in pure water；
2) with etc. the pure water of quality clean, refined filtration removal of impurities；
3) refined solution after refined filtration is freeze-dried to obtain the aluminum sulfate purified of fine white powder.
The HPLC chromatogram of aluminum sulfate is as shown in Figure 1 after purification, it is seen that the purity of aluminum sulfate after purification has before relatively purifying
Larger raising.Being freeze-dried obtained aluminum sulfate has more preferable dissolubility.
With reference to experiment, technical scheme is further illustrated.
Safety experiment：
Experimental Animal Center experiment portion of safety experiment commission Zhongshan University is carried out, experimental design reference：
1. the tertiary cloud of Xu, the pharmacological experimental methodology third edition
2.2014 editions medicine safety pharmacology investigative technique guidelines.
Specific experiment method is as follows：
Experiment material
Aluminum sulfate, molecular formula：Al2(SO4)3·18H2O, molecular weight：666.4.
First, acute toxicity test
1. test objective：
Observe aluminum sulfate after single is given in certain time whether caused toxic reaction, for the preliminary poison for understanding medicine
Property effect and its toxicity target organ, provide foundation for follow-up clinical test.
2nd, experimental animal and rearing conditions
SPF levels kunming mice 40,20 ± 2g, male and female half and half.Animal productiong supplying unit：In Zhongshan University experimental animal
Heart production department, experimental animal production licence number are：SCXK (Guangdong) 2011-0029, animal quality verification of conformity：
No.440085000 buys the date：On 08 15th, 2016；Animal identification method：With saturation picric acid by animal different parts
Fur applies dye and represents different animals number, and different animal husbandry cages is made a distinction with animal feeding load card mark.Raising temperature
20~26 DEG C of degree；Humidity 40RH%~70RH%；Rate of ventilation：Receptacle is more than 15 times/hour；Stocking density：Group support, per cage
Not more than 6.Use feed：The large and small mouse pellet of SPF levels, provided by Beijing Ke Ao Co., Ltds.Control group and administration group
Pets are as shown in Figure 2.
3rd, experimental method：Mouse is randomly divided into control group and administration group, it is specific as follows：
Table 4, acute toxicity test packet and dosage
| Group | Medicine | Dosage (mg/kg) | Capacity is administered | Size of animal |
| Control group | Physiological saline | / | 0.2ml/10g bw | 10 female 10 heros |
| Administration group | Aluminum sulfate solution | 2000 | 0.2ml/10g bw | 10 female 10 heros |
The compound method of aluminum sulfate solution is：Physiological saline 5ml, peace of the injection equipped with aluminum sulfate are accurately extracted with syringe
In cuing open, mix 10~20min of standing and fully dissolve to obtain.
Method of administration：Gastric infusion.
Administration frequency and observing time：Gastric infusion 1 time, observation post administration 14 days.
Testing index：Clinical observation：The general symptom of observation animal daily；Measured body weight：In administration D0, D3, D7, D14
Weigh the weight of animals；Organ coefficient determines：In the 15th day put to death animal, anatomic observation main organs abnormal conditions, core, liver,
5 spleen, lung, kidney internal organs are weighed.
Result treatment and analysis：Handled with statistic software SPSS 24, calculate the average weight and organ coefficient of two groups of animals
And make comparisons.
Experimental result：
During experiment, control group, administration group have no dead mouse and shown no obvious abnormalities.
Administration group the weight of animals is compared with control group, and there was no significant difference, refers to table 5.
The comparison of table 5, acute toxicity mouse weight
Organ coefficient statistical result refers to table 6.
The comparison of table 6, acute toxicity mice organs coefficient
* no significant difference (the P compared with control group<0.05) mouse all survives, and none is dead.
Conclusion：
Aluminum sulfate has preferable security, dosage 2000mg/kg, 0.2ml/10g bw0,2ml/10gbw physiology
Salt solution, have no obvious toxic-side effects.
Cells Gastric Cardiac Carcinoma growth inhibition check experiment
Experiment commission Hunan Province's Experimental Animal Center (Drug Safety Evaluation Center of Hunan Province) is carried out.
1st, experiment material
1.1 tested material：Compound is prepared：Aluminum sulfate 9g is weighed, adds 0.9% sodium chloride injection 15ml, and vibrate extremely
All dissolvings, produce 600mg/ml aluminum sulfate solutions, and this is maximum concentration working solution, will be standby after mother liquor progress bacteria removing.
1.2 positive control drug：Cis-platinum (DDP), lot number：SJJMI-IE, Tokyo HuaCheng Industry Co., Ltd；5 FU 5 fluorouracil
(5-FU), lot number：HFBM160120325008, Amresco company.Positive control drug is prepared：DDP or 5-FU2mg is weighed, with new
Fresh complete medium is configured to 100mM mother liquor, then mother liquor is configured to fresh complete medium 200 successively, 60,20,6,
2nd, 0.6 μM of working solution.
1.3 main material：
1.4 key instrument：
2nd, test method
2.1 cell culture
The MFC cells covered with are taken, using the DMEM in high glucose complete medium containing 10%FBS, in 37 DEG C, 5%CO2Culture
Cultivated in case, according to cell growth status, 1~2d is passed on or changed liquid, standby to exponential phase.
2.2CCK-8 methods detect cell proliferation test
Take the logarithm the phase growth MFC cells with every hole 5 × 103Individual cell is inoculated in 96 porocyte culture plates, treats that 12h is thin
After born of the same parents are adherent, vehicle control group, positive control drug (DDP) group, positive control drug (5-FU) group, aluminum sulfate group (0.3- are set
300mg/ml), every group of 5 multiple holes.Vehicle control group with fresh DMEM culture medium incubated cells completely, aluminum sulfate group respectively with containing
The fresh DMEM incubated cells completely of final concentration of 0.3-300mg/ml aluminum sulfate, DDP and 5-FU groups are respectively with containing final concentration of
100th, the fresh DMEM incubated cells completely of 30,10,3,1,0.3 μM of compounds.By after above-mentioned processing mode incubated cell 72h
The μ l of CCK-8 10 are added in per hole, continue to cultivate the absorbance for using ELIASA to measure each hole at 450nm after 1h.With solvent pair
It is 100% cell viability according to group OD values, the ratio of remaining each group OD values and vehicle control group OD values is relative activity.Increased with cell
Grow inhibiting rate and evaluate compound to the toxicity of MFC cells, if having cell proliferation inhibition rate ＞ 100%, be judged to instrument
Systematic error, based on 100%.
The detection of 2.3 Apoptosis
2.3.1 the double dye method detection Apoptosis of Annexin V-FITC and PI
The MFC cells in exponential phase are taken, conventional digestion collects cell, with 5 × 105The density in/hole is seeded to 6 holes
In plate, after 12h cell attachments, vehicle control group, aluminum sulfate group (10,30,100mg/ml), every group of 5 multiple holes are set.Solvent
Control group with fresh DMEM culture medium incubated cells completely, compound group respectively with containing final concentration of 10,30,100mg/ml chemical combination
The fresh DMEM incubated cells completely of thing.After 6h, conventional digestion collects cell, adds 500 μ l Binding Buffer buffer solutions
Cell is resuspended, cell is transferred in 1.5ml EP pipes, 5 μ l Annexin V-FITC, 5 μ l PI are added, in room temperature lucifuge bar
15min is incubated under part, with flow cytomery apoptosis situation.
2.3.2 fluorescence colour detects Apoptosis
Cell is handled according to 2.3.1 methods, after compound handles 6h, adds Hoechst 33342 per hole in 6 orifice plates
Dyeing liquor 1ml, fully covers cell, is placed in 37 DEG C of culture 20-30min.Dyeing liquor is discarded, glimmering after being washed 2-3 times with PBS
Fluoroscopic examination is carried out under light microscope.
Influence of the 2.4 Flow cytometry compounds to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell cycle
The MFC cells in exponential phase are taken, conventional digestion collects cell, with 5 × 105The density in/hole is seeded to 6 holes
In plate, after 12h cell attachments, vehicle control group, aluminum sulfate group (100,30,10mg/ml), every group of 5 multiple holes are set.Solvent
Control group with fresh DMEM culture medium incubated cells completely, aluminum sulfate group respectively with containing final concentration of 10,30,100mg/ml chemical combination
The fresh DMEM incubated cells completely of thing.After 6h, conventional digestion collects cell, is fixed overnight with 70% cold ethanol, adds 5 μ l's
PI, room temperature lucifuge is incubated 30min, with the flow cytomery cell cycle.
2.5 statistical analysis
Data are handled using the statistical softwares of SPSS 16.0, measurement data withRepresent, the ratio of two sample averages
Examined compared with using Student T-Test, the comparison of mean is using One-way ANOVA inspections, P between multisample group<0.05 represents
It is statistically significant, P<0.01 represents that examined difference is very significant.
3rd, evaluation of result
The influence that 3.1 aluminum sulfate are bred to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell
After the compound processing cell of micro- Microscopic observation various concentrations, there is cell proliferation rate and slow down, cell fragment
Increase, space between cells increases, phenomena such as shape of sand vacuole occurs in cell.Incubation time has clear and definite correlation to cell state together,
About after 12h is co-cultured, being rounded occurs in cell, the phenomenon of shrinkage；After 24h is co-cultured, there is part cell and swell, cell is saturating
Photosensitiveness is deteriorated, intercellular gap increase；After 48h is co-cultured, there is shape of sand vacuole in cell, the situations such as cell rupture occurs；
After 72h is co-cultured, shape of sand vacuole like cell substantially completely ruptures, without complete under 300,100,30mg/ml concentration conditions
The cell of cellular morphology, only see and be condensed into stain shape on a small quantity.Cell co-cultures with test sample or positive control drug DDP and 5-FU
After 72h, cell propagation is substantially suppressed, and has concentration-effect relation, with significant difference compared with vehicle control group
(P<0.01).Cell inhibitory effect is the results detailed in Table 7.
The influence that table 7, different compounds are bred to Mouse Stomach squamous cell carcinoma (orifice of the stomach position)
Note：* represent compared with vehicle control group, P<0.05, * * expressions are compared with vehicle control group, P<0.01.IC50Represent
Suppress the concentration of 50% tumour cell, Emax represents the maximal percentage inhibition to tumour cell.
Aluminum sulfate is as shown in Figure 3 to concentration-inhibiting rate curve of Mouse Stomach squamous cell carcinoma (orifice of the stomach position).
The influence that aluminum sulfate is bred to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC cells is as shown in figure 4, arrow represents bad
Dead cell.From the figures it is clear that aluminum sulfate can promote Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC downright bad.
Influence of 3.2 aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) apoptosis
Use concentration for 10,30, after 100mg/ml compound intervenes Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell 6h,
Cell is collected, Apoptosis is detected after the double dyes of Annexin V-FITC/PI.Cell after double dyes can be divided into 4 by flow cytometer
Group：Q1-UL represents mechanical damage cell (Annexin V-/PI+)；Q1-UR non-viable apoptotic cells (Annexin V+/PI+)；
Q1-LL survivaling cells (Annexin V-/PI-)；Q1-LR viable apoptotic cells (Annexin V+/PI-).Experimental result such as table 8
It is shown：
The influence of table 8, aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) apoptosis
Note：* represent compared with vehicle control group, P<0.05, * * expressions are compared with vehicle control group, P<0.01.
As a result show：The MFC cells late apoptic and non-viable non-apoptotic cell number handled through aluminum sulfate is apparently higher than vehicle control group
(P<0.05), and there is concentration-effect relation.
Influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC apoptosis is as shown in Figure 5；In figure, A is solvent pair
According to group, B is aluminum sulfate 10mg/ml groups, and C is aluminum sulfate 30mg/ml groups, and D is aluminum sulfate 100mg/ml groups；
Influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) MFC apoptosis is as shown in fig. 6, arrow represents nucleus
Shrinkage, prompt for apoptotic cell.
Influence of 3.3 aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cycle
Use concentration for 10,30, after 100mg/ml aluminum sulfate intervenes Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell 6h,
Cell is collected, after being fixed with 70% cold ethanol, after PI dyeing, the flow cytometry analysis cell cycle.The experimental result such as institute of table 9
Show.
The influence of table 9, aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) the MFC cell cycles
Note：* represent compared with vehicle control group, P<0.05, * * expressions are compared with vehicle control group, P<0.01.
As a result show：After aluminum sulfate processing, G0/G1Cell proportion substantially increases, G2/ M phase ratios significantly reduce, and show it
To Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell MFC inhibited proliferations mainly by Mouse Stomach squamous cell carcinoma (orifice of the stomach position)
Cell block is in G0/G1Phase, it is prevented to enter the S phases.
Influence of the aluminum sulfate to Mouse Stomach squamous cell carcinoma (orifice of the stomach position) the MFC apoptosis cycles is as shown in Figure 7；In figure, A is molten
Matchmaker's control group, B are aluminum sulfate 10mg/ml groups, and C is aluminum sulfate 30mg/ml groups, and D is aluminum sulfate 100mg/ml groups.
In summary, under this experiment condition, aluminum sulfate can significantly inhibit Mouse Stomach squamous cell carcinoma (orifice of the stomach position) cell
Propagation, and there is concentration-effect relation, under a high concentration condition, with the extension of time, cancer cell can be killed completely,
It can be by cell-cycle arrest in G0/G1Phase, inducing cell apoptosis.This compound performance suppression cancer cell concentration is higher, is mg/
Ml levels, may be related to its distinctive mechanism of action.The compound may directly act on tumor cell surface, and it is thin can to change cancer
It the physiological characteristic of born of the same parents, after cell surface aggregation, can effectively change the protein structure of cell surface, cause cell surface and thin
The albumen precipitation of matrix, causing cell permeability degradation, space between cells is shunk, and reduces the splitting ability of tumour cell,
The effectively propagation of control cell and transfer.After compound enters into the cell, the hydrolysis of cancer cells secrete multiple proteins can be suppressed
It enzyme, can be bonded directly in the DNA of cancer cell, cause DNA cracking, and effectively suppress the metabolism work(of cancer cell mitochondria
Can, with reference to the succinate dehydrogenase in mitochondria, change its biological effect, cause Cell microstructure to change, disabling signal
Path, the growth metabolism of tumour cell is disturbed, induced tumor Apoptosis, realizes the effect for killing cancer cell.
Described above is only the preferred embodiment of the present invention, it is noted that for the common skill of the art
For art personnel, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications
Also within protection scope of the present invention.
Claims (10)
1. aluminum sulfate is preparing the application in treating orifice of the stomach cancer drug.
2. application according to claim 1, it is characterised in that：The formulation of medicine is oral formulations.
3. application according to claim 2, it is characterised in that：Oral formulations are selected from tablet, capsule, granule, liquid
Preparation.
4. the application according to Claims 2 or 3, it is characterised in that：Oral formulations are sustained release preparation.
5. application according to claim 1, it is characterised in that：Aluminum sulfate is selected from the hydrate of aluminum sulfate.
A kind of 6. medicine for treating cardia cancer, it is characterised in that：Its active component includes aluminum sulfate.
7. medicine according to claim 6, it is characterised in that：Aluminum sulfate is aluminum sulfate more than food-grade, or using such as
Lower method purifies to obtain：
1) by aluminum sulfate and ultra-pure water mixed dissolution, aluminum sulfate solution is obtained；
2) refined filtration is carried out to aluminum sulfate solution, freeze-drying obtains aluminum sulfate freeze-dried powder.
8. medicine according to claim 7, it is characterised in that：The mass mixing ratio of aluminum sulfate and ultra-pure water is 1：(2~
5) the ultra-pure water purifying, used after dissolving.
9. medicine according to claim 7, it is characterised in that：The mass mixing ratio of aluminum sulfate and ultra-pure water is 1：3, dissolving
The ultra-pure water purifying of quality such as use afterwards.
10. according to the medicine described in claim 7,8 or 9, it is characterised in that：Using the filter membrane that aperture is 0.22 μm to aluminum sulfate
Solution carries out refined filtration.
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