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论文类型：期刊论文

发表时间：2016-08-09

发表刊物：ONCOTARGET

收录刊物：SCIE、PubMed、Scopus

卷号：7

期号：32

页面范围：51955-51964

ISSN号：1949-2553

关键字：HCC; ST6Gal-I; docetaxel; apoptosis; p38 MAPK

摘要：The beta-galactoside a2-6-sialyltransferase 1 (ST6Gal-I) is the principal sialyltransferase responsible for the addition of a2-6-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.