DOXORUBICIN RESISTANCE IN HUMAN-MELANOMA CELLS - MDR-1 AND GLUTATHIONE-S-TRANSFERASE-PI GENE-EXPRESSION

作者：RAMACHANDRAN C; YUAN ZK; HUANG XL; KRISHAN A

来源：Biochemical Pharmacology, 1993, 45(3): 743-751.

DOI：10.1016/0006-2952(93)90150-U

Cellular drug resistance is believed to involve P-glycoprotein-related drug efflux as well as xenobiotic detoxification. In the present study, we analyzed five human melanoma cell lines with 1- to 6-fold doxorubicin resistance for doxorubicin retention and MDR-1 and GST pi gene expression. All the cell lines had high doxorubicin retention, and efflux blockers such as trifluoperazine and verapamil did not have a major effect on drug retention or cytotoxicity. Even though all the cell lines carried the MDR-1 and GST pi genes, gene amplification was not associated with drug resistance. Both laser flow cytometry and immunoperoxidase staining showed high expression of C-219 reactive P-glycoprotein in some of the resistant cells which was not accompanied by either high drug efflux or sensitivity to doxorubicin efflux blockers.

• 出版日期1993-2-9