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Long-Term Cisplatin Exposure Promotes Methylation of the OCT1 Gene in Human Esophageal Cancer Cells |
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| Authors: | Rui Lin Xiaoli Li Jiansheng Li Lianfeng Zhang Feng Xu Yanjun Chu Jichang Li |
| Institution: | 1. Department of Gastroenterology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China 2. Institute of Clinical Medical Research of Universities in Henan Province, 1 East Jianshe Road, Zhengzhou, 450052, Henan, People’s Republic of China 3. Department of Gerontology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China |
| Abstract: | BackgroundCisplatin-based chemotherapy is widely used for treatment of a variety of human malignant solid and metastatic tumors, including esophageal cancer. However, the clinical effect of this drug is limited because of intrinsic and acquired resistance to it. Organic cation transporters (OCTs) are important in the cellular uptake of cisplatin.AimOur objective was to test the hypothesis that cisplatin resistance is associated with alteration of expression of OCTs.MethodsLevels of expression of OCTs in paired esophageal cancer and adjacent non-cancerous tissues were examined by use of immunohistochemistry.ResultsWe found that OCT1 silencing impaired cisplatin-mediated apoptosis of esophageal cancer cells. The level of OCT1 mRNA in cisplatin-resistant cells was markedly reduced compared with parental cells. Promoter methylation of OCT1 was induced in cisplatin-resistant cells.ConclusionThis study shows that long-term exposure to cisplatin promotes methylation of the OCT1 gene in human esophageal cancer cells, which in turn results in cisplatin resistance. |
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