title: Epithelial-mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin.
abstract: Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial-mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
authors.forename: Jun Li
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
authors.forename: Gan Lu
authors.initials: GL
authors.lastname: Deng
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008. hongshen2000@yahoo.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000071250:Snail Family Transcription Factors; D000077150:Oxaliplatin
keywords: Drug resistance; Epithelial–mesenchymal transition; Hepatocellular carcinoma; Oxaliplatin