ST6Gal-I modulates docetaxel sensitivity in human hepatocarcinoma cells via the p38 MAPK/caspase pathway
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Xixi Chen1,*, Liping Wang2,*, Yujie Zhao2, Shiqi Yuan2, Qiang Wu2, Xiaoling Zhu2, Bachir Niang2, Shujing Wang2, Jianing Zhang1
1School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, Liaoning, China
2Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China
*These authors have contributed equally to this work
Shujing Wang, email: [email protected]
Jianing Zhang, email: [email protected]
Keywords: HCC, ST6Gal-I, docetaxel, apoptosis, p38 MAPK
Received: September 11, 2015 Accepted: June 07, 2016 Published: June 21, 2016
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.
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