Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute Anticancer Drug Screen.

摘要: Identifying new chemotherapeutic agents and characterizing mechanisms of resistance may improve cancer treatment. The Anticancer Drug Screen the National Cancer Institute uses 60 cell lines to identify agents. Expression mdr-1/P-glycoprotein was measured by quantitative PCR. detected in 39 lines; highest levels were renal colon carcinomas. also all melanomas central nervous system tumors, but only one ovarian carcinoma leukemia line. Using a modified version COMPARE program, high correlation found between expression mdr-1 cellular large number compounds. Evidence that these compounds are P-glycoprotein substrates includes: (a) enhancement cytotoxicity verapamil; (b) demonstration cross-resistance multidrug-resistant line, (c) ability antagonize P-glycoprotein, increasing vinblastine accumulation decreasing efflux; (d) inhibition photoaffinity labeling azidopine. Identification many heretofore unrecognized as indicates has broader substrate specificity than previously recognized. This study confirms validity this novel approach provides basis for similar studies examining diverse group gene products, including other mechanisms, putative drug targets, genes involved cycle apoptosis.