Multidrug resistance in rat colon carcinoma cell lines CC531, CC531mdr+ and CC531rev.
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 microM 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+.
Gheuens
E
E
Laboratory of Cancer Research and Clinical Oncology, Antwerp University, Wilrijk, Belgium.
van der Heyden
S
S
Elst
H
H
Eggermont
A
A
Van Oosterom
A
A
De Bruijn
E
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D003630:Daunorubicin / Q000378:metabolism; D004351:Drug Resistance; D008562:Membrane Glycoproteins / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D003630:Daunorubicin