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Medicine combination for overcoming drug resistance of liver cancer and kidney cancer tumors and application of medicine combination

A technology of tumor drugs and anti-tumor drugs, applied in the field of biomedicine, can solve problems such as poor treatment effect, achieve the effect of improving drug efficacy and application range, and improving sensitivity

Active Publication Date: 2020-07-17
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many kinds of inhibitors developed targeting the histone methyltransferase EZH2 that have entered clinical trials (such as GSK-126). Such inhibitors have certain effects in the treatment of hematological tumors. Ineffective treatment of solid tumors

Method used

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  • Medicine combination for overcoming drug resistance of liver cancer and kidney cancer tumors and application of medicine combination
  • Medicine combination for overcoming drug resistance of liver cancer and kidney cancer tumors and application of medicine combination
  • Medicine combination for overcoming drug resistance of liver cancer and kidney cancer tumors and application of medicine combination

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1 Acetylation modification of EZH2 can enhance its stability

[0051] 1. Experiment 1:

[0052] Cells treated with acetylation inhibitor TSA were lysed with IP lysate, and protein quantification was performed by BCA protein quantification method. Lysine acetylation antibodies were added to the lysates of the lysis control group (DMSO) and the TSA treatment group, respectively, and incubated overnight at 4°C with slow shaking. Then take an appropriate amount of protein A / G magnetic beads, overnight incubation of the cell lysate and protein A / G magnetic beads. Then, centrifuge at 4°C and 500g for 1 minute, remove the supernatant lysate, wash 3 times with 500uL lysate, finally add 30µL of 2×SDS loading buffer, heat at 95°C for 10 minutes, centrifuge, and collect the supernatant sample . Samples were subjected to western blot analysis.

[0053] The results proved that the hepatocyte HL7702 was treated with 0.2 μM acetylase inhibitor (TSA) for 24 hours, and the a...

Embodiment 2

[0064] Example 2 Combined use of the acetylase inhibitor Anacardic Acid to enhance the killing sensitivity of the EZH2 activity inhibitor GSK-126 to liver and kidney cancer cells

[0065] 1. Experiment 1:

[0066]To detect the inhibitory effect of EZH2 inhibitor GSK126 on liver cancer and kidney cancer cells. Liver cancer SNU449 and SNU475 and kidney cancer RCC10 and A498 cell lines with logarithmic growth were inoculated into 96-well plates at 1000 cells per well, and the inoculated plates were placed in a cell culture incubator overnight. After 24 hours, the cells were treated with GSK-126 after the cells adhered to the wall, and the drug concentration was 0, 1, 2, 4, 6, 8 and 10 μM in gradients, and each group had three replicate wells. After GSK-126 treatment for 6 days, the CCK-8 solution and the medium were diluted 1:10, then the medium in the 96-well plate was removed, 100 μL of the CCK-8 dilution was added, and incubated in a 37°C incubator for 2 hours. The absorbanc...

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Abstract

The invention discloses a medicine combination for overcoming drug resistance of liver cancer and kidney cancer tumors and an application of the medicine combination. The research of the invention shows that through combined use of an acetylase inhibitor anacardic acid (AA) and an EZH2 inhibitor GSK-126, tumor sensitivity of the EZH2 inhibitor is enhanced from two aspects of reducing stability ofthe EZH2 and inhibiting activity of the EZH2, the effect is obvious, and a new method and a new idea are provided for improving the drug effect and the application range of the EZH2 inhibitor. Experiments show that combined use of the acetylase inhibitor and the EZH2 inhibitor has strong killing effect on hepatocellular carcinoma and renal clear cell carcinoma cells, and the effect of combined useis obviously superior to the effect of single use of the EZH2 inhibitor, so that combined use of the acetylase inhibitor and the EZH2 inhibitor can really exert a synergistic effect, and a new methodis provided for improving the drug effect and application range of the EZH2 inhibitor.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a drug combination for overcoming drug resistance of liver cancer and kidney cancer tumors and its application. Background technique [0002] Among the multiple human malignancies in the world, hepatocellular carcinoma (HCC) and clear cell renal cell carcinoma (ccRCC) rank among the top in terms of morbidity and mortality. However, the current drug treatment for these two tumors has the problem of drug resistance, which is the main reason for the frequent recurrence of tumors. [0003] Targeted therapy is an important conventional treatment in cancer treatment. The research, development and application of targeted drugs are the main content and purpose of targeted therapy. EZH2 (enhancer of zeste homolog 2) together with SUZ12 and EED constitute the PRC2 (Polycomb Repressive Complex 2) protein complex, which mainly undergoes trimethylation of the 27th lysin...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61P35/00A61K31/497A61K31/192
CPCA61K31/192A61K31/497A61K45/06A61P35/00A61K2300/00
Inventor 李博廖昆邓舒烨杨晴杨时雨
Owner SUN YAT SEN UNIV
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