Influence of Synuclein-γ on the Effectiveness of Antimicrotubule Drugs in Human Hepatoma Cells and the Mechanism
|School||Beijing Union Medical College|
|Course||Microbial and Biochemical Pharmacy|
|Keywords||Hepatoma cells SNCG Synuclein Microtubules Drug action HCC tissues VCR Cytoskeletal HCC Mechanisms Advanced hepatocellular carcinoma Mitosis Human hepatoma cell line Expression levels Resistance mRNA Liver cancer patients The treatment of liver cancer Drug treatment Cancer chemotherapy|
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, the annual mortality rate among the top three overall cancer mortality. Currently, paclitaxel (PTX) and vincristine (VCR), anti-microtubule drug as a target cell cycle specific drugs tubulin, has been widely used in the clinical treatment of advanced hepatocellular carcinoma metastasis and recurrence . However, the efficacy of these drugs for liver cancer patients vary widely, an important reason for liver cancer cells against microtubule drug resistance. Therefore, it was found to affect the cells of the anti-microtubule drug action within the factor has the significance. Nerve synuclein family members synuclein-γ (SNCG) in hepatocellular carcinoma and high expression, and the expression level was positively correlated with liver cancer pathological grade. SNCG cells can inhibit the function of the mitotic checkpoint kinase BubR1, resulting in abnormal cell division. Therefore, SNCG in hepatoma cells by inhibiting the activation of the mechanism of normal mitotic checkpoint may reduce liver cancer cells against the microtubule drug sensitivity, the impact of anti-microtubule drug efficacy. Its molecular mechanism of liver cancer cells in anti-microtubule drug effects in order to study the SNCG human hepatoma cell line SMMC-7721 and HepG2 stable expression of synuclein-γ (SNCG) model to predict anti-SNCG as detected at the cellular level. molecular markers microtubule drug treatment of hepatocellular carcinoma and its liver cancer treatment the possibility as well as the significance of the new target. SNCG generally high expression in HCC tissues and hepatoma cells. Real-time quantitative PCR (Real-time RT-PCR) and Western blot assay (Western blotting) confirmed build SNCG overexpression significant increase in mRNA and protein levels in the cell model. PTX or VCR, treated separately, and significantly reduce its SNCG overexpression hepatoma cell growth inhibition. SNCG overexpression can reduce the anti-microtubule drug-induced cell mitotic arrest, liver cancer SMMC-7721 cells and HepG2 PTX, the VCR drug sensitivity significantly reduced. Whole genome expression microarray detection results suggest that, SNCG can affect the cell cycle regulation of cytoskeleton, cell migration and cell resistance cell regulatory pathways associated gene (AREG EREG of ATF3,, MMP2, DUSP5, ALDH3A1 IGFBP1, IFI16) expression is governed by the SNCG the impact of the change. Comprehensive experimental results, SNCG in hepatoma cells overexpression significantly reduce its effectiveness against the microtubule drug sensitivity, SNCG potential anti-microtubule drug use biomarkers in liver cancer chemotherapy. SNCG play a key role in the spindle assembly checkpoint pathway, so that it expected to become the new target of liver cancer with treatment.