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Recently, the team of Professor Zeng Su from Zhejiang University School of Pharmacy has made important progress in regulating the DNA methylation mechanism of drug transporter expression and its use in reversing tumor drug resistance. Paper Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin Published on July 20th at Science Translational Medicine.
It is understood that the Zengsu team first discovered that DNA methylation plays an important role in the decline of the expression of organic cation transporter 2 (OCT2) in renal cell carcinoma. The study found that DNA methylation inhibits the binding of MYC protein to the E-box site, thereby preventing histone methyltransferase MLL1 from being written into histone H3K4 trimethylation, reducing histone methylation levels, thereby inhibiting OCT2. Gene transcription.
Based on this mechanism, the researchers designed a sequential combination of the DNA methyltransferase inhibitor decitabine (DAC) and the OCT2 substrate anticancer drug oxaliplatin (Oxa). Through experimental research, the expression level of OCT2 in the kidney cancer tissues of the tumor-bearing mice after the administration of decitabine was significantly increased, resulting in a large increase in the accumulation of oxaliplatin in the renal cell carcinoma, thereby exerting a significant anti-tumor effect. The experiment also showed that the expression of multidrug and toxic compound efflux transporter 2K (MATE-2K) was also significantly decreased in renal cell carcinoma, and decitabine could not induce an increase in its expression, which made Oxali into renal cancer cells. Platinum is not easily excreted by MATE-2K. The researchers found that OCT2 and MATE-2K are highly expressed in normal kidney cells, and oxaliplatin entering renal cancer cells can be excreted into the urine by MATE-2K without accumulation, making oxaliplatin normal. Kidney tissue is less toxic.
The results have positive significance for the treatment of renal cell carcinoma, and provide ideas for the treatment of other innate drug-resistant tumors, which is known as "Opening a door into cancer cells" in the industry.
The project was funded by the National Natural Science Foundation of China.
Zhejiang University School of Pharmacy has made important progress in reversing tumor drug resistance research
[China Pharmaceutical Network Technology News] It is reported that the team of Professor Zeng Su from Zhejiang University School of Pharmacy has made important progress in reversing tumor resistance research, and found for the first time that DNA methylation has decreased the expression of organic cation transporter 2 (OCT2) in renal cell carcinoma. Importantly, this finding has positive implications for the treatment of renal cell carcinoma.