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. 1993 Nov;84(11):1201–1208. doi: 10.1111/j.1349-7006.1993.tb02822.x

Multidrug Resistance in Rat Colon Carcinoma Cell Lines CC531, CC531mdr+ and CC531rev

Eric Gheuens 1, Sylke van der Heyden 1, Hilde Elst 1, Alexander Eggermont 1, Allan Van Oosterom 1, Ernst De Bruijn 1,✉
PMCID: PMC5919088  PMID: 7903965

Abstract

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 μM 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 multidrugresistant variant CC531mdr+.

Keywords: Multidrug resistance, P‐gp, Colon carcinoma, Rat cell line, CDDP‐resistance

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