[Vincristine-resistant human KB cell line and mechanism of multidrug resistance].
A multidrug-resistant (mdr) clone of human cancer KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, KBv200, obtained after ethylmethane sulfonate (EMS) mutagenesis showed 175-fold higher resistance to vincristine than did KB cells. The cells were also cross-resistant to taxol, colchicine and adriamycin. Cellular accumulation of vincristine in KBv200 was decreased to less than one-fifth of that in KB. To determine the presence of mdr 1 mRNA in KBv200 and KB, total cellular RNAs from each cell line were analyzed by means of slot blot hybridization. The result showed that the mdr 1 gene had been highly expressed in KBv200. In addition, verapamil, a calcium channel blockers, was shown to increase VCR accumulation in KBv200 and reverse the vincristine resistance. All these results demonstrate that the mechanism of KBv200 cell resistance to multiple drugs resulted from increased expression of mdr 1 gene and brought about over production of P-glycoprotein and increased the efflux of drugs.
Institute of Materia, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing.
X H
XH
Zhang
F Y
FY
Zhang
X J
XJ
Ji
Z Y
ZY
Li
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D004351:Drug Resistance; D018432:Drug Resistance, Multiple; D015870:Gene Expression; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014750:Vincristine; D014700:Verapamil