title: The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma.
abstract: Tumor invasion and chemotherapy resistance, which are associated with epithelial-mesenchymal transition (EMT), remain as major challenges in hepatocellular carcinoma (HCC) treatment. Neferine, a natural component of Nelumbo nucifera, have been proven the antitumor efficiency in cancer, but the effects of Neferine on HCC invasion and chemosensitivity need to be elucidated. Applying multiple assays of cell proliferation, flow cytometry, immunofluorescence staining, qRT-PCR, Western blot, fluorescence molecular tomography imaging, the influences of Neferine on EMT-regulated viability, apoptosis, invasion, and oxaliplatin (OXA) sensitivity were assessed in HCC cells of HepG2 and Bel-7402, as well as in xenograft animal models in vivo. Here, we reported that Neferine had no obvious effects on HCC cells proliferation, but significantly enhanced cytotoxicity and apoptosis caused by OXA in vitro and in vivo. Through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin, Neferine suppressed EMT-induced migration and invasion abilities of HCC cells. TGF-β1 cancelled the effects of Neferine on the migration and invasion of HCC cells. Snail overexpression or TGF-β1-induced EMT attenuated Neferine-mediated OXA sensitization in HCC. Together, our data suggest that Neferine enhances oxaliplatin sensitivity through an inhibition of EMT in HCC cells. Neferine may be used as an OXA sensitizer in HCC chemotherapy.
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Ganlu
authors.initials: G
authors.lastname: Deng
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yin
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Cai
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.|Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; 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; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D009944:Organoplatinum Compounds; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; D000077150:Oxaliplatin; C057222:neferine