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Application of FAK inhibitor in preparation of SHP2 inhibitor sensitizing drug

An inhibitor, FAK technology, applied in the field of biomedicine to achieve the effect of improving drug sensitivity

Inactive Publication Date: 2020-09-15
THE NAVAL MEDICAL UNIV OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a new SHP2 inhibitor sensitization solution for the problem of drug resistance of CRC cells to SHP2 inhibitors in the prior art, to study the mechanism leading to SHP099 drug resistance

Method used

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  • Application of FAK inhibitor in preparation of SHP2 inhibitor sensitizing drug
  • Application of FAK inhibitor in preparation of SHP2 inhibitor sensitizing drug
  • Application of FAK inhibitor in preparation of SHP2 inhibitor sensitizing drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 3

[0041] Example 3. Combination medication inhibits AKT signal feedback activation

[0042] SHP099 and PF573228 (10 μM) were combined to treat SW620 and Colo205 cells, and Western blot was used for detection. The specific process is as follows:

[0043] (1) Cell plating

[0044] Take target cells in good growth state to make cell suspension, use 6-well plate to plate, cell density is 3×10 5 cells / well, then add 2 mL of cell suspension to each well, and transfer to the cell culture incubator smoothly and gently to continue culturing. The next day, after the cells adhered to the wall, the culture medium was removed, the control group was added with ordinary culture medium, and the experimental group was added with corresponding concentrations of liquid medicine, such as SW620 cells (SHP099 40 μM+PF573228 10 μM) and Colo205 cells (SHP099 30 μM+PF573228 10 μM), both 2mL.

[0045] (2) Protein extraction

[0046] After the above treatment for 1h, 3h, 12h, 24h, place the cells on i...

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Abstract

The invention relates to the technical field of biomedical engineering, and provides an application of an FAK inhibitor in preparation of an SHP2 inhibitor sensitizing drug, especially an applicationof the FAK inhibitor in preparation of a colorectal cancer SHP2 inhibitor sensitizing drug. An experiment verifies that an FAK inhibitor can eliminate the drug resistance phenomenon of an SHP2 inhibitor; and after the two inhibitors jointly act, feedback activation of AKT signals after SHP2 inhibition can be universally eliminated, the AKT signals are further inhibited, and the effect of obviouslysynergistically killing tumor cells is achieved, for example, the clone formation capacity of CRC cells and the growth speed of colorectal cancer bodies can be remarkably inhibited. Therefore, the invention provides new exploration for improving sensitivity of the SHP2 inhibitor, is beneficial to improving drug sensitivity of malignant tumors, and has a certain clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of FAK inhibitors in the preparation of SHP2 inhibitor sensitization drugs and the sensitization drug composition containing the same. Background technique [0002] Colorectal cancer (CRC) is a common malignant tumor in the gastrointestinal tract, and its morbidity and mortality are second only to gastric cancer, esophageal cancer and primary liver cancer among digestive system malignant tumors. According to statistics, there are more than 1.8 million new CRC patients in the world every year, accounting for 10.2% of all cancer cases. [0003] At present, drug chemotherapy is a commonly used clinical treatment, especially for patients with advanced CRC. Targeted therapy has become a hot spot in cancer treatment in recent years. Targeted drugs combined with chemotherapy can significantly prolong the survival of patients and improve their quality of life. SHP2,...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/497A61K31/506A61K31/5377A61P35/00A61P35/02
CPCA61K45/06A61K31/497A61K31/506A61K31/5377A61P35/00A61P35/02A61K2300/00
Inventor 张凡常文军李晔傅亚婷朱伊娜袁浩
Owner THE NAVAL MEDICAL UNIV OF PLA
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