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with HCC are diagnosed at a late stage when the curative treatment of surgical resection and liver transplantation are no longer applicable.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.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / genetics
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ATP Binding Cassette Transporter, Subfamily B / metabolism
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Antineoplastic Agents / pharmacology*
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Apoptosis
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COP9 Signalosome Complex
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Cyclin-Dependent Kinase 6 / genetics
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Cyclin-Dependent Kinase 6 / metabolism
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Drug Resistance, Neoplasm*
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Gene Expression
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Hep G2 Cells
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Humans
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Integrin beta1 / genetics
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Integrin beta1 / metabolism
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / genetics
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Multidrug Resistance-Associated Proteins / metabolism
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NF-kappa B / physiology
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Niacinamide / analogs & derivatives*
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Niacinamide / pharmacology
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Peptide Hydrolases / genetics*
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Peptide Hydrolases / metabolism
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Phenylurea Compounds / pharmacology*
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RNA, Small Interfering / genetics
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Signal Transduction
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Sorafenib
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Transforming Growth Factor beta1 / physiology
Substances
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ABCB1 protein, human
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ABCC2 protein, human
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Antineoplastic Agents
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CCND1 protein, human
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Integrin beta1
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Intracellular Signaling Peptides and Proteins
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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NF-kappa B
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Neoplasm Proteins
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Phenylurea Compounds
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RNA, Small Interfering
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Transforming Growth Factor beta1
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Cyclin D1
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Niacinamide
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Sorafenib
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CDK6 protein, human
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Cyclin-Dependent Kinase 6
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Peptide Hydrolases
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COPS5 protein, human
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COP9 Signalosome Complex