Abstract
The effect of the antibiotic agent novobiocin on the sensitivity of melanoma cells to colchicine and vinblastine was examined in drug-sensitive and drug-resistant B16 melanoma cells. A cell line COL/R was selected for colchicine resistance. The COL/R cell line (resistant to 80 ng/ml colchicine) was found to possess the multidrug-resistant (MDR) phenotype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine accumulation was markedly decreased in COL/R cells as compared to the parental B16 cells. Verapamil reversed drug resistance and increased rhodamine accumulation in COL/R cells. Novobiocin in combination with colchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased colchicine resistance and increased rhodamine accumulation. These data show that novobiocin incrases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.
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Abbreviations
- PGP:
-
P glycoprotein
References
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Nordenberg, J., Kornfeld, J., Wasserman, L. et al. Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells. J Cancer Res Clin Oncol 120, 599–604 (1994). https://doi.org/10.1007/BF01212814
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DOI: https://doi.org/10.1007/BF01212814