Increased mdr gene expression and decreased drug accumulation in a human colonic cancer cell line resistant to hydrophobic drug.
An adriamycin-resistant human colonic cancer cell line was characterized. This clone exhibits the classical multidrug resistance (MDR) phenotype, being cross-resistant to hydrophobic drugs such as colchicine, and vinblastine. In contrast, this clone shows a normal response to DNA-damaging agents. The appearance of MDR in these cells was linked to a decreased accumulation of the drug [3H]colchicine as compared to the drug-sensitive cells. This MDR line expressed 80-100 fold increased levels of the specific 4.5-kb mdr mRNA, and a gene amplification. Our results indicate that MDR in human colonic cancer cells can result from increased expression of at least one member of the mdr gene family.
Chao
C C
CC
Tumor Biology Laboratory, Department of Biochemistry, Chang Gung Medical College, Taiwan, Republic of China.
Ma
C M
CM
Cheng
P W
PW
Lin-Chao
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D003078:Colchicine / Q000378:metabolism / Q000494:pharmacology; D003110:Colonic Neoplasms; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008937:Mitomycins; D012333:RNA, Messenger; D011691:Puromycin; D016685:Mitomycin; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D003078:Colchicine