title: CSN5 silencing reverses sorafenib resistance of human hepatocellular carcinoma HepG2 cells.
abstract: Hepatocellular carcinoma (HCC) is one of the most common tumor types, and is the third leading cause of cancer mortalities worldwide. A large number of patients with HCC are diagnosed at a late stage when the curative treatment of surgical resection and liver transplantation are no longer applicable. Sorafenib has been proved to improve overall survival in advanced HCC; however, drug resistance is common. The present study reported that the CSN5 is correlated with sorafenib resistance of the HCC cell line HepG2/S. Following silencing of CSN5, resistance to sorafenib was reversed, and multi-drug‑resistance proteins, including as adenosine triphosphate binding cassette (ABC)B1, ABCC2 and ABCG2 as well as CDK6, cyclin D1 and B‑cell lymphoma 2 were downregulated. In addition, it was demonstrated that the integrin beta-1, transforming growth factor‑β1 and nuclear factor‑κB pathways were modified by CSN5.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Tianjin Hospital, Tianjin 300211, P.R. China.
authors.forename: Zhengyao
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Tianjin Entry‑Exit Inspection and Quarantine Bureau, International Travel Healthcare Center, Tianjin 300456, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Xibo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Che
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Jianheng
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Junjian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery (2), Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000077157:Sorafenib; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000075686:COP9 Signalosome Complex; D019938:Cyclin D1; D051361:Cyclin-Dependent Kinase 6; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009536:Niacinamide; D010447:Peptide Hydrolases; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; D000077157:Sorafenib; D053773:Transforming Growth Factor beta1; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C530104:CCND1 protein, human; C495911:CDK6 protein, human; C501488:COPS5 protein, human