title: ST6Gal-I modulates docetaxel sensitivity in human hepatocarcinoma cells via the p38 MAPK/caspase pathway.
abstract: The β-galactoside α2-6-sialyltransferase 1 (ST6Gal-I) is the principal sialyltransferase responsible for the addition of α2-6-sialic acid to the termini N-glycans on cell surface. Although ST6Gal-I in cancer cell resistance to chemotherapeutics agents has been previously reported, the role of ST6Gal-I in clinical drug resistance of hepatocellular carcinoma (HCC) is not fully understood. In this study, we found that knockdown of ST6Gal-I increased the sensitivity of hepatocarcinoma MHCC97-H cells to docetaxel treatment by instigating the process of apoptosis. Silencing ST6Gal-I expression decreased the survival rate of MHCC97-H cells after docetaxel treatment. Importantly, ST6Gal-I silencing resulted in an increasing of phospho-p38, Bax, Bad, cytochrome c and the cleaved caspase-9, 3 and PARP, while a decreasing of the anti-apoptotic protein Bcl-2. In addition, we found that p38 MAPK and caspase-3 inhibitors can reduce the enhanced apoptosis levels of MHCC97-H cells resulted by either ST6Gal-I silencing or docetaxel treatment. Conversely, exogenous expression of ST6Gal-I in hepatocarcinoma Huh7 cells inhibited apoptotic cell death and prevented docetaxel-induced apoptosis by inhibiting p38 MAPK mediated mitochondrial-dependent pathway. Taken together, these results indicate that ST6Gal-I might play a positive role in mediating the survival of human hepatocarcinoma cells and could be a potential target for gene and antitumor drugs therapy.
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, Liaoning, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Bachir
authors.initials: B
authors.lastname: Niang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, Liaoning, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System; D012799:Sialyltransferases / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D020169:Caspases; D000077143:Docetaxel; D012799:Sialyltransferases; D043823:Taxoids; D048051:p38 Mitogen-Activated Protein Kinases; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: HCC; ST6Gal-I; apoptosis; docetaxel; p38 MAPK