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[耐药性人肺癌细胞内长春新碱的外排并非由P-糖蛋白介导]

[The efflux of intracellular vincristine in drug-resistant human lung cancer cells is not mediated by P-glycoprotein].

作者信息

Song E J, Chiang C D, Chao C C, Cheng V

机构信息

Department of Biology, Tunghai University, Taichung, Taiwan, R.O.C.

出版信息

J Formos Med Assoc. 1993 Jun;92 Suppl 2:S69-75.

PMID:7904199
Abstract

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.

摘要

通过体外暴露于长春新碱(VCR)衍生出的人肺腺癌细胞系(PC-9)的一个亚系(PC-9/VCR),经MTT和HTCA测定显示对VCR具有10至12倍的抗性。与亲代细胞系(PC-9)相比,PC-9/VCR抗性细胞对VCR的摄取减少。PC-9/VCR显示出VCR外排速率增强。与多药耐药不同,通过Northern印迹法测定,这种外排与P-糖蛋白过表达无关。此外,PC-9/VCR对维拉帕米无旁系敏感性。该抗性亚系对秋水仙碱和长春碱的交叉抗性分别仅为6.9倍和2.5倍。这一初步结果表明,PC-9/VCR中药物摄取缺陷是由于其他机制,可能涉及微管组装。

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J Formos Med Assoc. 1993 Jun;92 Suppl 2:S69-75.
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