ESTABLISHMENT OF DOXORUBICIN-RESISTANT SUBLINE DERIVED FROM HCT15 HUMAN COLORECTAL-CANCER CELLS

Doxorubicin, one of the clinically most useful anticancer agents, is u sed alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxo rubicin for anticancer drug. We newly established doxorubicin-resistan t HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon ca ncer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fol d of its parental cells, and it also revealed cross-resistance to acti nomycin D, etoposide and vinblastine but not to cisplatin and tamoxife n. And verapamil, a reversal agent of multidrug-resistance (MDR) by P- glycoprotein, elevated the cytotoxicity of doxorubicin against both HC T15 and HCT15/CL02 cells. But the relative resistant rate was not redu ced. Verapamil had no effects on the toxicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some fu nctionally complex mechanisms for MDR.