顺铂通过降低CTR1蛋白表达诱导人食管鳞状癌细胞系EC109产生耐药性
[Cisplatin induces drug resistance in human esophageal squamous carcinoma cell line EC109 by decreasing CTR1 protein expression].
作者信息
Yu Le, Chen Ming-hui, Gu Chun-ping, Li Yi-lei, Wen Jing, Fu Jian-hua, Cho Chi-hin, Liu Shu-wen
机构信息
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2011 May;31(5):801-4.
OBJECTIVE
To investigate the mechanism of the development of cisplatin resistance in a human esophageal squamous carcinoma cell line.
METHODS
The cytotoxicity of cisplatin in the cisplatin-resistant resistant cell line EC109/CDDP and its parental cell line EC109 was measured by MTT assay. Whole-cell cisplatin accumulation and Pt-DNA adduct formation were determined by inductively coupled plasma mass spectrometry (ICP-MS). Western blotting was used to investigate the protein expression of full length PARP, cleaved PARP, and copper transporter 1 (CTR1).
RESULTS
EC109/CDDP cells was more resistant to cisplatin-induced cytotoxicity and apoptosis than EC109 cells. Compared with EC109 cells, EC109/CDDP cells exhibited less cisplatin accumulation and Pt-DNA adduct formation with also decreased CTR1 protein expression.
CONCLUSION
Cisplatin induces drug resistant phenotype by decreasing the protein level of CTR1, which controls cell accumulation and cytotoxic effect of cisplatin.
目的
探讨人食管鳞状癌细胞系中顺铂耐药发生的机制。
方法
采用MTT法检测顺铂对顺铂耐药细胞系EC109/CDDP及其亲本细胞系EC109的细胞毒性。通过电感耦合等离子体质谱法（ICP-MS）测定全细胞顺铂蓄积量和铂-DNA加合物的形成。采用蛋白质印迹法研究全长PARP、裂解的PARP和铜转运蛋白1（CTR1）的蛋白表达。
结果
与EC109细胞相比，EC109/CDDP细胞对顺铂诱导的细胞毒性和凋亡更具抗性。与EC109细胞相比，EC109/CDDP细胞的顺铂蓄积量和铂-DNA加合物形成较少，CTR1蛋白表达也降低。
结论
顺铂通过降低CTR1蛋白水平诱导耐药表型，CTR1控制顺铂的细胞蓄积和细胞毒性作用。
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