Modulation of cisplatin sensitivity and accumulation by interferon alpha-2A in human squamous carcinoma cell lines.
Modulation of cisplatin sensitivity and accumulation by interferon alpha-2A in human squamous carcinoma cell lines.
复制标题
干扰素 α-2A 在人鳞状癌细胞系中调节顺铂敏感性和积累。
DOI：
10.1002/ijc.2910630320
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发表时间：
1995
影响因子：
6.4
通讯作者：
Singh,SV
中科院分区：
文献类型：
--
作者：
Gupta,V;Jani,JP;Emerson,EO;Xu,BH;Scalamogna,D;Xia,H;Katoh,A;Zaren,HA;Singh,SV
本研究旨在阐明干扰素α‐2a （IFN α‐2a）在人鳞状癌细胞系SCC‐25和SCC‐4中增强顺铂（CDDP）细胞毒性的机制。IFN α‐2a处理在两种细胞系中均以剂量依赖的方式显著增加CDDP的细胞毒性。在SCC‐25细胞中，用400和800 1U/ml IFN α‐2a处理细胞，CDDP的细胞毒性分别增加了约2倍和4倍。400和800 1U/ml IFN α‐2a处理后，SCC‐4细胞对CDDP的敏感性分别提高了约3倍和7倍。药物摄取实验显示，与相应的对照组相比，IFN α‐2a处理的细胞中铂的积累大约高出1.4 - 5倍。谷胱甘肽（GSH）和谷胱甘肽转移酶的细胞水平，被认为是肿瘤细胞对CDDP敏感性的重要决定因素，在两种细胞系中均未被IFN α‐2a治疗改变。Northern blot分析显示，经IFN α‐2a处理后，这些细胞中MT‐IIAmRNA水平适度升高（约30-40%）。我们的研究结果表明，IFN α‐2a‐介导的SCC‐25和SCC‐4细胞系对体外CDDPin的敏化可能是由于细胞内铂积累的增加。
This study was undertaken to elucidate the mechanism(s) of potentiation of cisplatin (CDDP) cytotoxicity by interferon α‐2a (IFN α‐2a) in human squamous carcinoma cell lines SCC‐25 and SCC‐4. IFN α‐2a treatment significantly increased the cytotoxicity of CDDP in both cell lines in a dose‐dependent manner. In SCC‐25 cells, the cytotoxicity of CDDP was increased by about 2‐ and 4‐fold, respectively, by treating the cells with 400 and 800 1U/ml IFN α‐2a. Sensitivity of SCC‐4 cells to CDDP was increased by about 3‐ and 7‐fold, respectively, by 400 and 800 1U/ml IFN α‐2a treatment. Drug uptake experiments revealed approximately 1.4‐ to 5‐fold higher platinum accumulation in IFN α‐2a‐treated cells as compared to respective controls. Cellular levels of glutathione (GSH) and GSH transferase, which have been suggested to be important determinants of tumor cell sensitivity to CDDP, were not altered by IFN α‐2a treatment in either of the cell lines. Northern blot analysis showed a moderate increase (about 30–40%) in the level of MT‐IIAmRNA by IFN α‐2a treatment in these cells. Our results suggest that IFN α‐2a‐mediated sensitization of SCC‐25 and SCC‐4 cell lines to CDDPin vitromay be due to an increase in intracellular platinum accumulation.