MULTIDRUG-RESISTANCE IN RAT COLON-CARCINOMA CELL-LINES CC531, CC531(MDR+) AND CC531(REV)

A rat colon carcinoma cell line, CC531, was exposed to stepwise increasing concentrations of colchicine. A cell line, CC531mdr+, which grows in the presence of 0.2 muM of colchicine was obtained. A revertant cell line, CC531rev was isolated upon colchicine withdrawal. The CC531mdr+ displayed a multidrug-resistant phenotype. Marked resistance to the selecting agent colchicine, was found (RF=37.5) as well as to vinblastine (RF=11.3) and actinomycin D (RF=2.6). Cross resistance to doxorubicin (RF=8) and daunorubicin (RF=13.3) was demonstrated. Verapamil was able to reverse drug resistance to colchicine and daunorubicin. The revertant cell line, CC531rev, showed increased sensitivity to colchicine (RF=0.43), vinblastine (RF=0.13), doxorubicin (RF=0.28) and daunorubicin (RF=0.56). Marked cross resistance to cis-platinum (RF=6.9) was also induced in CC531mdr+ and was maintained in CC531rev. We conclude that CC531 displays an intrinsic low-level multidrug-resistant phenotype, which was amplified in the CC531mdr+ variant. This correlates with a higher level of expression of P-glycoprotein. CC531rev lacks the multidrug-resistant phenotype and can be used as the drug-sensitive counterpart of the latter two cell lines. Furthermore, it has been shown that in these cell lines cis-platinum resistance is mediated through a mechanism independent of the multidrug-resistant phenotype, since the revertant cell line CC531rev has lost the multidrug-resistant phenotype while retaining the concomitantly induced cis-platinum resistance of the multidrug-resistant variant CC531mdr+.