Application of msh3 protein inhibitor in the preparation of drugs for reversing drug resistance of mtx drug-resistant tumor cells

A technology of protein inhibitors and tumor cells, which is applied in the application field of MSH3 protein inhibitors in the preparation of drugs that reverse the drug resistance of MTX-resistant tumor cells. It can solve the problems of DNA double-strand breaks and reconnection, and achieve the reversal of tumor resistance medicine, efficiency-enhancing effect

Active Publication Date: 2021-05-18
HARBIN MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

Although there are still many controversies about the formation mechanism of HSR and DMs, the essential events are the break and reconnection of DNA double strands.

Method used

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  • Application of msh3 protein inhibitor in the preparation of drugs for reversing drug resistance of mtx drug-resistant tumor cells
  • Application of msh3 protein inhibitor in the preparation of drugs for reversing drug resistance of mtx drug-resistant tumor cells
  • Application of msh3 protein inhibitor in the preparation of drugs for reversing drug resistance of mtx drug-resistant tumor cells

Examples

Experimental program
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Effect test

Embodiment 1

[0058]Cell culture

[0059]The human colon cancer cell line HT29 was continuously cultured by MTX increasing in concentration gradient, and a series of HT29MTX drug-resistant cells were screened. After each concentration gradient cells were tolerated to the corresponding drug concentration, it continued to cultivate 5 months until it stabilized Afterwards, continue subsequent experiments.

[0060]HT29 parent and drug-resistant cells were cultured in DMEM high sugar medium containing 15% fetal bovine serum, and the corresponding concentrations were added to the drug-resistant cell-based medium medium. All cells cultured in 5% CO2, 37 ° C thermostat cell incubator.

[0061]2. MMR key protein in HT29 parental cells and MTX-resistant cells

[0062]Test HT29 parental cells through Western Blot and the degree of tolerance to MTX is 10-4The expression level of MMR pathway key protein MSH3, MSH2, MSH6 and MLH1 in MMR passage of MMR pathway in MOL / L.

[0063](1) Extraction of total protein of cells

[0064]...

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Abstract

The invention discloses the application of an MSH3 protein inhibitor in the preparation of a drug for reversing the drug resistance of MTX drug-resistant tumor cells, and belongs to the technical field of medicine. The present invention is aimed at malignant tumor cells with MTX drug resistance and highly amplified DHFR gene, using MSH3 as the target, reducing the degree of gene amplification, reducing DMs and HSR in the cells, and at the same time, interfering with MSH3 can inhibit HR, NHEJ and A‑EJ The repair effect on DSBs can reverse tumor drug resistance and improve the efficiency of tumor treatment. The invention provides a new targeted treatment plan for the biological treatment of malignant tumors where MTX is used as the main therapeutic drug and is prone to drug resistance, and provides a scientific basis for effectively combating MTX drug resistance. In addition, the present invention also has very positive significance for in-depth understanding of the nature of chemotherapeutic drug resistance and finding drug resistance targets for individualized treatment.

Description

Technical field[0001]The present invention relates to the application of a MSH3 protein inhibitor in the preparation of drug resistance to MTX drug resistance, and more particularly to the MSH3 protein inhibitor to prepare a repair ability of the cell to DNA double strand breakage, and then the DHFR gene is amplified. The application of reversing tumor cells on drug resistance of MTX drug resistance is within the field of medical technology.Background technique[0002]Methotrexate, MTX is used as an anti-metabolic anti-tumor drug, which is widely used in acute lymphocytic leukemia, lymphoma, chlorinated epithelial carcinoma, breast cancer, head and neck cancer, bladder cancer and lung cancer. The MTX can be competed for the synthesis of dihydrofolate to form tetrahydrofluolic acid by competition, resulting in the synthesis of DNA, resulting in the synthesis of DNA, and finally causing cell death. However, some patients will produce acquaintance resistance during MTX treatment, causing...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/7088A61P35/00
CPCA61K31/7088A61K45/00A61P35/00
Inventor 孟祥宁王旭蔡梦迪朱静关荣伟高巍马金法王萍周静张涵威于森陈思宇
Owner HARBIN MEDICAL UNIVERSITY
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