| Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases with high mortality in China, and the third most common cause of cancer-related death worldwide. Currently, antimicrotubule drugs such as paclitaxel (PTX) and vincristine (VCR) are used as the common agents in the clinical chemotherapy for liver cancer. However, the responses of patients to these drugs vary markedly. Successful identification of intracellular factors influencing liver cancer's sensitivity to antimicrotubule drugs would be great clinical importance. Synuclein-y (SNCG) is the member of synuclein family (SNCs). Expression of SNCG is elevated in the HCC; and its expression is observed in a stage-specific manner. SNCG is shown to interact with BubR1, which is a key mitotic checkpoint kinase, and inhibit mitotic checkpoint control and confers cellular resistance to antimicrotubule drugs.In this study, by engineering human hepatoma cells SMMC-7721 and HepG2 to overexpress synuclein-y (SNCG), we investigated if SNCG is a molecular factor associated with the sensitivity to antimicrotubule drug treatment. Real-time RT-PCR and Western blotting assays showed that SNCG was successfully overexpressed in 7721/SNCG and HepG2/SNCG cells compared with mock-cells. The overexpressed SNCG also reduced sensitivity of the hepatoma cells to antimicrotubule drugs. Correspondingly, the hepatoma cells overexpressed SNCG showed higher resistance to PTX or VCR than mock-cells. Meanwhile, the SNCG-cells showed significantly lower mitotic index than mock-cells.Our studies suggested that the overexpression of SNCG could confer resistance to antimicrotubule drugs in hepatoma cells; and it indicated that SNCG may be as a potential response marker for antimicrotubule drugs in liver cancer thermotherapy. SNCG might be a key therapeutic target due to its prominent role in the spindle assembly checkpoint pathway. |
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