BACKGROUND: Cisplatin-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. AIM: Our objective was to test the hypothesis that cisplatin resistance is associated with alteration of expression of OCTs. METHODS: Levels of expression of OCTs in paired esophageal cancer and adjacent non-cancerous tissues were examined by use of immunohistochemistry. RESULTS: We 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. CONCLUSION: This 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.
BACKGROUND:Cisplatin-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. AIM: Our objective was to test the hypothesis that cisplatin resistance is associated with alteration of expression of OCTs. METHODS: Levels of expression of OCTs in paired esophageal cancer and adjacent non-cancerous tissues were examined by use of immunohistochemistry. RESULTS: We 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. CONCLUSION: This study shows that long-term exposure to cisplatin promotes methylation of the OCT1 gene in humanesophageal cancer cells, which in turn results in cisplatin resistance.
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