Cross-resistance of platinum derivatives in H-1R, a cisplatin-resistant cell line.
Cross-resistance of platinum derivatives in H-1R, a cisplatin-resistant cell line.
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DOI：
10.3892/or_00000243
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发表时间：
2009
期刊：
影响因子：
4.2
通讯作者：
K. Negoro;Yukio Yamano;D. Nakashima;Kengo Saito;Ken Nakatani;M. Shiiba;H. Bukawa;H. Yokoe;K. Uzawa;T. Wada;H. Tanzawa;S. Fujita
中科院分区：
文献类型：
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作者：
K. Negoro;Yukio Yamano;D. Nakashima;Kengo Saito;Ken Nakatani;M. Shiiba;H. Bukawa;H. Yokoe;K. Uzawa;T. Wada;H. Tanzawa;S. Fujita
我们以前建立了H-1 R细胞，顺铂（CDDP）耐药的细胞系，从H-1细胞，CDDP敏感的口腔癌细胞系。本研究的目的是确定H-1 R细胞对含铂剂的抗肿瘤药物交叉耐药的分子机制。3-（3，4-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）比色法和克隆形成实验表明，H-1 R细胞对卡铂、奈达铂和奥沙利铂有较强的交叉耐药。铜转运蛋白和有机阳离子转运蛋白的表达状态通过实时定量逆转录-聚合酶链反应进行确认。转运蛋白ATP 7A、ATP 7 B、hCtr 1、hOCT 1和hOCT 2表达上调，而hOCT 3表达下调。与H-1细胞相比，H-1 R细胞中的细胞谷胱甘肽水平升高2倍。我们的研究结果表明，H-1和H-1 R细胞可能是有用的，在寻找候选基因负责的交叉耐药铂衍生物和进一步的研究，以了解铂耐药的机制。
We previously established H-1R cells, a cisplatin (CDDP)-resistant cell line, from H-1 cells, a CDDP-sensitive oral carcinoma cell line. The aim of this study was to identify the molecular mechanism of cross-resistance to antitumor drugs containing a platinum agent in H-1R cells. The 3-(3,4-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and clonogenecity assay indicated that H-1R cells showed strong cross-resistance to carboplatin, nedaplatin and oxaliplatin. The expression status of the copper transporter and organic cation transporters was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. The transporters ATP7A, ATP7B, hCtr1, hOCT1 and hOCT2 were up-regulated, whereas hOCT3 was down-regulated. The cellular glutathione level was elevated 2-fold in H-1R cells compared with H-1 cells. Our results suggested that H-1 and H-1R cells may be useful in searching for candidate genes responsible for cross-resistance to platinum derivatives and for further studies to understand the mechanism of platinum resistance.