Doxorubicin resistance in human melanoma cells: MDR-1 and glutathione S-transferase pi gene expression.
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.
Ramachandran
C
C
Department of Radiation Oncology, University of Miami Medical School, FL 33136.
Yuan
Z K
ZK
Huang
X L
XL
Krishan
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression; D005982:Glutathione Transferase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007941:Leukemia P388 / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014268:Trifluoperazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014268:Trifluoperazine; D004317:Doxorubicin; D014700:Verapamil; D005982:Glutathione Transferase