CN106913571A - A kind of medicine and its application for treating tumour - Google Patents

A kind of medicine and its application for treating tumour Download PDF

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Publication number
CN106913571A
CN106913571A CN201710257848.6A CN201710257848A CN106913571A CN 106913571 A CN106913571 A CN 106913571A CN 201710257848 A CN201710257848 A CN 201710257848A CN 106913571 A CN106913571 A CN 106913571A
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CN
China
Prior art keywords
fluorouracil
methylcytisine
mixture
antineoplastic
medicine
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CN201710257848.6A
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Chinese (zh)
Inventor
高丽
王珂欣
秦雪梅
张丽增
杜冠华
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Shanxi University
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Shanxi University
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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine

Abstract

The invention discloses a kind of medicine for treating tumour and its application.Described medicine is N methylcytisines, or N methylcytisines and 5 fluorouracils mixture.The medicine can significantly inhibit the propagation of human liver cancer cell SMMC 7721 and murine lung cancer cell LLC.Compared with the classical fluorouracil of antineoplastic 5 is used alone, the N methylcytisines and 5 fluorouracil mixtures that the present invention is provided show more preferable antitumor action, with preferable application prospect and clinical reference value.

Description

A kind of medicine and its application for treating tumour
Technical field
The present invention relates to biomedicine technical field, a kind of medicine for treating tumour and its application are particularly belonged to.
Background technology
Liver cancer is one of popular ten kinds of malignant tumours of highest in the world, and the death rate occupies in alimentary system malignant tumour Second, the incidence of disease is on the rise, and the annual new cases of China account for the whole world more than half.The lung cancer morbidity rate of same China and The death rate is also in steeply rise trend.The essential therapeutic arsenals of tumour are surgical resection, radiotherapy, chemotherapy etc. now.But by The features such as tumour disease has easy recurrence, high malignancy, easily transfer, poor prognosis, independent chemotherapy and other local therapeutic approaches are past It is past to be unable to reach effective therapeutic purposes.
N-Methylcytisine (N-Methylcytisine), also known as N-methylcytisine, are that the methyl of sparteine takes For product, isolated and purified from legume trollflower, herba sophorae alopecuroide seed, its relative molecular weight is 327.37, molecular formula It is C19H21NO4.With anti-inflammatory and analgesic effect.
5 FU 5 fluorouracil (5-Fluorouracil, 5-FU) is clinically most widely used miazines cancer therapy drug, to liver Cancer, tumor in digestive tract and other solid tumors have good efficacy, and critical role is occupied in oncotherapy.But its toxicity is big, Medication effective dose is close with dosis toxica, normal cell is badly damaged while tumour cell is killed.With traditional change Synthetic drug is learned to compare, natural drug because its Small side effects, research cycle is short the advantages of favored, it is therefore increasing natural Compound is found and is applied in the generation evolution for suppressing Nasopharyngeal neoplasms.
Clinical research shows, can produce drug resistance using single antineoplastic for a long time.And Chinese medicine is same with chemotherapeutics Shi Yingyong can significantly increase anti-tumour cell proliferative effect, and reduce the toxicity of chemotherapeutics.Therefore, by natural drug and The mixture of chemotherapeutics is applied to suppress the strategy of tumor cell proliferation, for oncotherapy provides new thinking and direction.
The content of the invention
It is an object of the invention to provide the mixing of N-Methylcytisine and N-Methylcytisine and 5 FU 5 fluorouracil Application of the thing in antineoplastic is prepared.
Application of the N-Methylcytisine that the present invention is provided in anti-liver cancer and anti-lung cancer medicine is prepared.The N- methyl gold The concentration of sparrow flower alkali is 0.25-10mgmL-1；It is preferred that 0.5-5mgmL-1.Experimental study shows, 2,4mgml-1N- first Base sparteine can significantly inhibit the propagation of human liver cancer cells Hep G2, and inhibiting rate is respectively 23.77%, 41.15%； 0.5、1、2、4mg·ml-1N-Methylcytisine can significantly inhibit the propagation of murine lung cancer cell LLC, inhibiting rate is respectively 38.10%th, 48.25%, 63.49%, 79.51%.
Present invention simultaneously provides a kind of N-Methylcytisine and 5 FU 5 fluorouracil mixture prepare anti-liver cancer and anti-and lung Application in cancer drug.5 FU 5 fluorouracil concentration is 20 μ gmL in the mixture-1, N-Methylcytisine concentration is 1- 4mg·mL-1.Experimental study shows, 4mgmL-1N-Methylcytisine and 20 μ gmL-15 FU 5 fluorouracil mixture is to people The inhibiting rate of Hepatocellular carcinoma cell line is 74.30%；1mg·mL-1N-Methylcytisine and 20 μ g/mL-15- fluorine urine is phonetic Pyridine mixture is 61.93% to the inhibiting rate of murine lung cancer cell LLC.
A kind of antineoplastic that the present invention is provided, it is N-Methylcytisine；The N-Methylcytisine it is dense It is 0.25-10mgmL to spend-1；It is preferred that 0.5-5mgmL-1。
A kind of antineoplastic that the present invention is provided, it is the mixture of N-Methylcytisine and 5 FU 5 fluorouracil.Institute 5 FU 5 fluorouracil concentration is 20 μ gmL in stating mixture-1, N-Methylcytisine concentration is 1-4mgmL-1。
Beneficial effects of the present invention：Antineoplastic of the present invention can significantly inhibit human liver cancer cells Hep G2 and small The propagation of mouse lung carcinoma cell LLC.Compared with classical antineoplastic 5 FU 5 fluorouracil is used alone, N- methyl goldspink of the invention Flower alkali and 5 FU 5 fluorouracil mixture show more preferable antitumor action, with preferable application prospect.
Brief description of the drawings
The inhibitory action (24h) that Fig. 1 .N- methylcytisines are bred to SMMC-7721 cells；***P<0.001 and blank Control group is compared.
The inhibitory action (24h) that Fig. 2 .5- fluorouracils are bred to SMMC-7721 cells；***P<0.001 and blank Group is compared.
The inhibitory action that Fig. 3 .N- methylcytisines and 5 FU 5 fluorouracil mixture are bred to SMMC-7721 cells；**P< 0.01,***P<0.001 compared with blank control group；##P<0.01,###P<0.001 and N-Methylcytisine (4mgmL-1) and 5 FU 5 fluorouracil (20 μ gmL-1) mixture administration group compares；ΔP<0.05,ΔΔP<0.01 and N-Methylcytisine (2mg mL-1) and 5 FU 5 fluorouracil (10 μ gmL-1) mixture administration group compares.
The inhibitory action (24h) that Fig. 4 .N- methylcytisines are bred to LLC cells；**P<0.01,***P<0.001 with it is empty White control group is compared.
The inhibitory action (24h) that Fig. 5 .5- fluorouracils are bred to LLC cells；*P<0.05,**P<0.01 and blank Group is compared.
The inhibitory action (24h) that Fig. 6 .N- methylcytisines and 5 FU 5 fluorouracil mixture are bred to LLC cells；**P< 0.01,***P<0.001 compared with blank control group；##P<0.01 and N-Methylcytisine (1mgmL-1) and 5 FU 5 fluorouracil (20μg·mL-1) mixture administration group compares；ΔP<0.05 and N-Methylcytisine (0.5mgmL-1) and 5 FU 5 fluorouracil (10μg·mL-1) mixture administration group compares.
The suppression knot of Fig. 7 .N- methylcytisines, 5 FU 5 fluorouracil and mixture to SMMC-7721 cell migration abilities Really (24h)；
The inhibiting rate of Fig. 8 .N- methylcytisines, 5 FU 5 fluorouracil and mixture to SMMC-7721 cell migration abilities (24h)；**P<0.01,***P<0.001 compared with blank control group；#P<0.05,##P<0.01 and N-Methylcytisine (2mg mL-1) and 5 FU 5 fluorouracil (10 μ gmL-1) mixture administration group compares.
Specific embodiment
In order to further be described in detail to the present invention, specific examples below is provided, but only conduct illustrates this Invention, rather than in order to limit the scope of the present invention.
Embodiment 1
N-Methylcytisine and its suppression bred to SMMC-7721 cells and LLC cells with 5 FU 5 fluorouracil mixture Make and use, wherein the concentration of mixture selects each compound IC50Concentration near value.
N-Methylcytisine is determined using mtt assay and its is lived with the suppression of 5 FU 5 fluorouracil mixture cell proliferation Property.By logarithmic phase cell with 5 × 104Individual/hole is inoculated in 96 orifice plates, after culture 24h, adds corresponding pastille nutrient solution, every group If 6 multiple holes.After continuing to cultivate 24h, the culture medium containing MTT is changed in every hole, after being incubated 4h with 37 DEG C, abandoning supernatant, 100 μ L DMSO solutions, dissolving purple crystal precipitation are added to vibrate 10min, operation repetitive 6 times per hole.With ELIASA in 490nm Place determines its absorbance (OD values), calculates cell survival rate and half-inhibition concentration (IC50)。
As Figure 1-3, N-Methylcytisine (4mgmL-1) and 5 FU 5 fluorouracil (20 μ gmL-1) mixture It is 74.30% to the inhibiting rate of SMMC-7721 cells, hence it is evident that higher than individually giving 4mgmL-1N-Methylcytisine and individually Give 20 μ gmL-1To the inhibiting rate of SMMC-7721 cells, (inhibiting rate is respectively 46.34% He during 5 FU 5 fluorouracil 41.15%)；N-Methylcytisine (2mgmL-1) and 5 FU 5 fluorouracil (10 μ g/mL-1) mixture it is thin to SMMC-7721 The inhibiting rate of born of the same parents is 29.80%, hence it is evident that higher than individually giving 2mgmL-1N-Methylcytisine and individually give 20 μ gmL-1To the inhibiting rate (inhibiting rate is respectively 23.77% and 13.38%) of SMMC-7721 cells during 5 FU 5 fluorouracil.
As Figure 4-Figure 6, N-Methylcytisine (1mgmL-1) and 5 FU 5 fluorouracil (20 μ gmL-1) mixture It is 61.93% to the inhibiting rate of LLC cells, hence it is evident that higher than individually giving 1mgmL-1N-Methylcytisine and 20 μ gmL- 1To the inhibiting rate (inhibiting rate is respectively 48.25% and 51.49%) of LLC cells during 5 FU 5 fluorouracil；N-Methylcytisine (0.5mg·mL-1) and 5 FU 5 fluorouracil (10 μ gmL-1) mixture to the inhibiting rate 55.11% of LLC cells, hence it is evident that be higher than Individually give 0.5mgmL-1N-Methylcytisine and 10 μ gmL-1To the inhibiting rate (suppression of LLC cells during 5 FU 5 fluorouracil Rate processed is respectively 38.10% and 52.30%).
Further investigate N-Methylcytisine (2mgmL-1) and 5 FU 5 fluorouracil (10 μ gmL-1) mixture pair The transcellular inhibiting rates of SMMC-7721, to inquire into its potentiality applied in anti-liver cancer and anti-field.
Embodiment 2
N-Methylcytisine and its influence with 5 FU 5 fluorouracil mixture to SMMC-7721 cell migration abilities.
SMMC-7721 cell suspensions are with 5 × 104Individual/hole is inoculated in 6 orifice plates, after 100% converges, exhausts nutrient solution, adds PBS liquid is washed 1 time, along the standardized straight line in orifice plate bottom, the cell for scraping is washed away with PBS, adds the culture containing different pharmaceutical concentration Base, control group adds the culture medium containing same concentrations DMSO, and taking 4 at random respectively after culture 12,24,36h, under microscope regards Open country, the distance between each time point cut hecatomeral cells is measured using NIS-Elements imaging softwares, is used to represent tumour cell Transfer ability.
Experimental result such as Fig. 7, shown in 8, as a result shows in 0h, administration group compared with blank control group migration distance without obvious Influence, after 36h is administered, blank control group cell there occurs apparent migration, and cut distance narrows；10μg·mL-15- fluorine Uracil group and 2mgmL-1N-Methylcytisine group cell migration ability is inhibited, and cut healing rate slows down；But When giving N-Methylcytisine (2mgmL-1) and 5 FU 5 fluorouracil (10 μ gmL-1) mixture after, can substantially suppress thin The transfer ability of born of the same parents.And healing rate has significant difference with blank control group and compared with being administered alone group.

Claims (10)

  1. Application of the 1.N- methylcytisines in antineoplastic is prepared.
  2. 2. application of the N-Methylcytisine as claimed in claim 1 in antineoplastic is prepared, the tumour is lung cancer Or liver cancer.
  3. 3. application of the N-Methylcytisine as claimed in claim 1 in antineoplastic is prepared, the N- methyl goldspink The concentration of flower alkali is 0.25-10mgmL-1。
  4. 4. a kind of antineoplastic, it is characterised in that it is N-Methylcytisine.
  5. 5. medicine as claimed in claim 4, the concentration of the N-Methylcytisine is 0.25-10mgmL-1。
  6. Application of the mixture of 6.N- methylcytisines and 5 FU 5 fluorouracil in antineoplastic is prepared.
  7. 7. the mixture of N-Methylcytisine as claimed in claim 6 and 5 FU 5 fluorouracil in antineoplastic is prepared should With the tumour is lung cancer or liver cancer.
  8. 8. the mixture of N-Methylcytisine as claimed in claim 6 and 5 FU 5 fluorouracil in antineoplastic is prepared should With 5 FU 5 fluorouracil concentration is 20 μ gmL in the mixture-1, N-Methylcytisine concentration is 1-4mgmL-1。
  9. 9. a kind of antineoplastic, it is the mixture of N-Methylcytisine and 5 FU 5 fluorouracil.
  10. 10. medicine as claimed in claim 9,5 FU 5 fluorouracil concentration is 20 μ gmL in the mixture-1, N- methyl goldspinks Flower alkali concn is 1-4mgmL-1。
CN201710257848.6A 2017-04-19 2017-04-19 A kind of medicine and its application for treating tumour Pending CN106913571A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109172569A (en) * 2018-09-13 2019-01-11 淮安亿泰生物科技有限公司 A kind of alkaloid compound for preventing and treating patients with lung cancer cisplatin-resistant
CN109172571A (en) * 2018-09-13 2019-01-11 淮安亿泰生物科技有限公司 A kind of alkaloid is used to reverse the purposes of lung cancer cisplatin-resistant
CN109200050A (en) * 2018-09-13 2019-01-15 淮安亿泰生物科技有限公司 Application of the alkaloid in terms of reversing lung cancer cisplatin-resistant

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KOTIYA D等: "Role of PXR in Hepatic Cancer: Its Influences on Liver Detoxification Capacity and Cancer Progression", 《PLOS ONE》 *
WANG LY等: "The Chinese Herbal Medicine Sophora flavescens Activates Pregnane X Receptor", 《DRUG METABOLISM AND DISPOSITION》 *
ZHANG LS等: "A Functional Polymorphism in the 3-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker", 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》 *
黄峻等: "《临床药物手册》", 31 January 2015 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109172569A (en) * 2018-09-13 2019-01-11 淮安亿泰生物科技有限公司 A kind of alkaloid compound for preventing and treating patients with lung cancer cisplatin-resistant
CN109172571A (en) * 2018-09-13 2019-01-11 淮安亿泰生物科技有限公司 A kind of alkaloid is used to reverse the purposes of lung cancer cisplatin-resistant
CN109200050A (en) * 2018-09-13 2019-01-15 淮安亿泰生物科技有限公司 Application of the alkaloid in terms of reversing lung cancer cisplatin-resistant
CN109200050B (en) * 2018-09-13 2020-11-20 普瑞赛森(山东)生物医学科技有限公司 Application of alkaloid in reversing drug resistance of lung cancer cisplatin
CN109172569B (en) * 2018-09-13 2020-12-22 浙江亚瑟医药有限公司 Alkaloid compound for preventing and treating cisplatin resistance of lung cancer patient
CN109172571B (en) * 2018-09-13 2021-03-02 泉州智慧果技术服务有限公司 Application of alkaloid in reversing drug resistance of cisplatin in lung cancer

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Application publication date: 20170704