Open AccessMultidrug Resistance in Rat Colon Carcinoma Cell Lines CC531, CC531 mdr + and CC531 rev
Author(s) -
Gheuens Eric,
Heyden Sylke,
Elst Hilde,
Eggermont Alexander,
Oosterom Allan,
Bruijn Ernst
Publication year - 1993
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1993.tb02822.x
Subject(s) - multiple drug resistance , vinblastine , p glycoprotein , doxorubicin , colchicine , cancer research , medicine , cell culture , chemotherapy , drug resistance , biology , microbiology and biotechnology , genetics
A rat colon carcinoma cell line, CC531, was exposed to stepwise increasing concentrations of colchicine. A cell line, CC531 mdr + , which grows in the presence of 0.2 μ M of colchicine was obtained. A revertant cell line, CC531 rev was isolated upon colchicine withdrawal. The CC531 mdr + 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, CC531 rev , 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 CC531 mdr + and was maintained in CC531 rev . We conclude that CC531 displays an intrinsic low‐level multidrug‐resistant phenotype, which was amplified in the CC531 mdr + variant. This correlates with a higher level of expression of P‐glycoprotein. CC531 rev 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 CC531 rev has lost the multidrug‐resistant phenotype while retaining the concomitantly induced cis ‐platinum resistance of the multidrugresistant variant CC531 mdr + .