Impact of O6-methylguanine-DNA methyltransferase expression on the drug resistance of clear cell renal cell carcinoma

Abstract

Objective: The deoxyribonucleic acid-repair protein O6-methylguanine-deoxyribonucleic acid methyltransferase is a major determinant of resistance of cells to various alkylating drugs. Its expression profile is different in different cancer types. Here, we studied the expression and function of O6-methylguanine-deoxyribonucleic acid methyltransferase in clear cell renal cell carcinoma. Methods: The expression of O6-methylguanine-deoxyribonucleic acid methyltransferase was evaluated in clear cell renal cell carcinoma tissues and cell lines by quantitative real-time polymerase chain reaction and immunohistochemistry. The relationship between O6-methylguanine-deoxyribonucleic acid methyltransferase expression and clinicopathological characteristics was analyzed. To further investigate the function of O6-methylguanine-deoxyribonucleic acid methyltransferase in clear cell renal cell carcinoma resistance to alkylating agents, siRNA targeting O6-methylguaninedeoxyribonucleic acidmethyltransferasewere used to silence the O6-methylguanine-deoxyribonucleic acid methyltransferase expression. Results: We found that O6-methylguanine-deoxyribonucleic acidmethyltransferase is over-expressed in clear cell renal cell carcinoma tissues and cell lines. O6-methylguanine-deoxyribonucleic acid methyltransferase expression is related with tumor progression in clear cell renal cell carcinoma patients. Up-regulation of O6-methylguanine-deoxyribonucleic acid methyltransferase plays a critical role in primary resistance to alkylating agents. Conclusions: The overexpression of O6-methylguanine-deoxyribonucleic acid methyltransferase contributes to resistance of clear cell renal cell carcinoma to standard chemotherapy. Our results have significance for understanding a new pathway of the development of drug resistance of clear cell renal cell carcinoma.