[The efflux of intracellular vincristine in drug-resistant human lung cancer cells is not mediated by P-glycoprotein].
A subline (PC-9/VCR) of the human lung adenocarcinoma cell line (PC-9), derived by in vitro exposure to vincristine (VCR), exhibited a 10-12-fold resistance to VCR by MTT and HTCA assay. Compared to the parental cell line (PC-9), PC-9/VCR-resistant cells displayed a reduced accumulation of VCR. The rate of VCR efflux was shown to be enhanced by PC-9/VCR. Unlike multidrug resistance, this efflux was independent of P-glycoprotein overexpression as determined by the Northern blotting method. In addition, PC-9/VCR showed no collateral sensitivity to verapamil. This resistant subline only showed 6.9-fold and 2.5-fold cross resistance to colchicine and vinblastine, respectively. This preliminary result indicates that defective drug accumulation in PC-9/VCR is due to other mechanisms possibly involving the microtubule assembly.
Song
E J
EJ
Department of Biology, Tunghai University, Taichung, Taiwan, R.O.C.
Chiang
C D
CD
Chao
C C
CC
Cheng
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000473:pathology*; D002352:Carrier Proteins / Q000502:physiology*; D004351:Drug Resistance; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014750:Vincristine / Q000493:pharmacokinetics* / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine