Reversal of thermochemotherapeutic resistance to rhodamine 123 by verapamil.
Rhodamine 123 (R123) cytotoxicity and intracellular accumulation were studied at elevated temperature in R123-sensitive and R123-resistant B16 mouse melanoma cell lines. Hyperthermic potentiation of R123 cytotoxicity, present in the parental R123-sensitive cell line, was not present in the R123-resistant cell line. R123-resistant melanoma cells did not develop concomitant resistance to hyperthermia. Hyperthermic potentiation of R123 cytotoxicity was restored in the resistant cells by co-treatment with verapamil. Restoration of hyperthermic potentiation of R123 by verapamil in R123-resistant cells was accompanied by increased intracellular accumulation and decreased efflux of R123. These results suggest that verapamil may be used to re-establish thermal enhancement of drug cytotoxicity when thermochemotherapeutic resistance is present.
Krag
D N
DN
Department of Surgery, University of California, Davis, Medical Center, Sacramento 95817.
Théon
A P
AP
Gan
L
L
Shen
T S
TS
Wardell
J
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004351:Drug Resistance; D006358:Hot Temperature; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000628:therapy; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D012235:Rhodamines; D020112:Rhodamine 123; D014700:Verapamil