Mechanism of cross-resistance to cisplatin in a mitomycin C-resistant human bladder cancer cell line.
Mechanism of cross-resistance to cisplatin in a mitomycin C-resistant human bladder cancer cell line.
复制标题
丝裂霉素 C 耐药人膀胱癌细胞系对顺铂的交叉耐药机制。
DOI：
10.1002/ijc.2910610326
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发表时间：
1995
影响因子：
6.4
通讯作者：
Blanock,K
中科院分区：
文献类型：
--
作者：
Singh,SV;Xu,BH;Jani,JP;Emerson,EO;Backes,MG;Rihn,C;Scalamogna,D;Stemmler,N;Specht,S;Blanock,K
本研究旨在阐明丝裂霉素C（MMC）耐药人膀胱癌细胞系J82/MMC对顺铂（CDDP）交叉耐药的机制。与亲本J82/WT细胞相比，J82/MMC细胞系显示出对CDDP和卡铂的2 - 3倍交叉耐药性。药物摄取研究表明，J82/MMC细胞系中对CDDP的交叉耐药性与铂蓄积减少无关。与J82/WT细胞相比，J82/MMC细胞系对氯化镉的抗性约为1.5倍，氯化镉是金属硫蛋白（MT）含量增加的指标。北方印迹分析显示，与J82/WT相比，J82/MMC细胞系中MT-IIAmRNA的水平高2.7倍。我们之前已经报道过，尽管这些细胞中的谷胱甘肽（GSH）水平相当，但与J82/WT相比，J82/MMC细胞系中的GSH转移酶（GST）活性显著更高。本研究结果表明，J82/MMC细胞系中GST活性升高是由于π型GST蛋白的过表达。尽管丁硫氨酸-S，R-亚砜亚胺（BSO）诱导的GSH耗竭显著增强了两种细胞系中的CDDP细胞毒性，但J82/MMC细胞中的增强幅度（约2.1倍）明显高于J82/WT（约1.6倍）。我们的研究结果表明，在J82/MMC细胞系中对CDDP的交叉耐药性可能是由于细胞巯基的改变。©1995 Wiley利斯公司
This study was undertaken to elucidate the mechanism(s) of cross‐resistance to cisplatin (CDDP) in a mitomycin C (MMC)‐resistant human bladder cancer cell line, J82/MMC. The J82/MMC celi line displayed 2‐ to 3‐fold cross‐resistance to CDDP and carboplatin when compared to the parental J82/WT cells. Drug uptake studies revealed that cross‐resistance to CDDP in the J82/MMC cell line was independent of reduced platinum accumulation. The J82/MMC cetl line exhibited approximately a 1.5‐fold resistance to cadmium chloride, an indicator for increased metallothionein (MT) content, when compared to the J82/WT cells. Northern blot analysis showed a 2.7‐fold higher level of MT‐IIAmRNA in the J82/MMC ceil line compared with J82/WT. We have reported previously that, whereas glutathi‐one (GSH) level is comparable in these cells, GSH transferase (GST) activity is significantly higher in the J82/MMC eell line compared with J82/WT. Results of the present study showed that the elevated GST activity in the J82/MMC cell line was due to an over‐expression of π‐type GST protein. Although buthio‐nine‐S,R‐sulfoximine (BSO)‐induced GSH depletion significantly enhanced CDDP cytotoxicrty in both cell lines, the magnitude of potentiation was markedly higher in J82/MMC cells (about 2.1‐fold) relative to J82/WT (about 1.6‐fold). Our results suggest that cross‐resistance to CDDP in the J82/MMC cell tine may be due to alterations in cellular thiols. ©1995 Wiley‐Liss, Inc.