Long-term cisplatin exposure promotes methylation of the OCT1 gene in human esophageal cancer cells.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Gastroenterology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Rui
R
Lin
Xiaoli
X
Li
Jiansheng
J
Li
Lianfeng
L
Zhang
Feng
F
Xu
Yanjun
Y
Chu
Jichang
J
Li
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D016133:Polymerase Chain Reaction / Q000379:methods; D000099254:Organic Cation Transporter 3
D000970:Antineoplastic Agents; D002945:Cisplatin; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D000099254:Organic Cation Transporter 3; C491013:SLC22A2 protein, human