title: MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer.
abstract: This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas.
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital Yinchuan 750002, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, People's Republic of China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, People's Republic of China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital Yinchuan 750002, People's Republic of China.
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital Yinchuan 750002, People's Republic of China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital Yinchuan 750002, People's Republic of China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D019014:fas Receptor / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D002945:Cisplatin; D053222:Fas Ligand Protein; D027501:Monocarboxylic Acid Transporters; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D027981:Symporters; D019014:fas Receptor; D000099233:Monocarboxylate Transport Protein 1; C491901:FAS protein, human; C505661:FASLG protein, human; C516742:PTPN13 protein, human; C505407:CASP3 protein, human
keywords: Fas; MCT1; cisplatin-resistant; epithelial ovarian cancer