Cisplatin induces drug resistance in human esophageal squamous carcinoma cell line EC109 by decreasing CTR1 protein expression / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism of the development of cisplatin resistance in a human esophageal squamous carcinoma cell line.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Cisplatin induces drug resistant phenotype by decreasing the protein level of CTR1, which controls cell accumulation and cytotoxic effect of cisplatin.</p>