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肝癌是中国最常见的恶性肿瘤之一。目前,紫杉醇(paclitaxel,PTX)和长春新碱(vincristine,VCR)等抗微管药物是临床上肝癌化疗的常用药物,然而此类药物对患者的疗效差别很大。因此,发现影响抗微管药物作用的细胞内因子具有重要意义。本研究采用人肝癌细胞株HepG2稳定过表达synuclein-γ(SNCG)模型,研究SNCG是否影响肿瘤细胞对抗微管药物的敏感性。实时定量PCR(real-timeRT-PCR)和蛋白免疫印迹(Western blotting)法检测HepG2/SNCG细胞稳定高表达SNCG,与HepG2/Neo细胞相比,SNCG mRNA表达上调13.6倍,增殖活性增高(66±5)%。经PTX或VCR分别处理,SNCG过表达可降低抗微管药物诱导的细胞有丝分裂期阻滞,HepG2/SNCG细胞的G2/M期比例较HepG2/Neo细胞分别下降(19±2.9)%和(27±1.7)%;HepG2/SNCG、HepG2/Neo和HepG2细胞对PTX的有丝分裂指数分别为0.47、0.64和0.67,对VCR的有丝分裂指数分别为0.14、0.30和0.34。HepG2/SNCG细胞对PTX、VCR的敏感性显著降低,耐药指数分别为21和15。研究结果表明,SNCG在肝癌细胞过表达后可显著降低其对抗微管药物的敏感性,在肝癌化疗中SNCG是潜在的抗微管药物使用的生物标志物。
Liver cancer is one of the most common malignancies in China. Currently, anti-microtubule drugs such as paclitaxel (PTX) and vincristine (VCR) are commonly used in clinical chemotherapy of hepatocellular carcinoma. However, the efficacy of these drugs in patients varies greatly. Therefore, it is of great significance to find intracellular factors that affect the anti-microtubule drug effects. In this study, human hepatocellular carcinoma cell line HepG2 was stably overexpressed in the synuclein-γ (SNCG) model to investigate whether SNCG affects the sensitivity of tumor cells to anti-microtubule drugs. Compared with HepG2 / Neo cells, the expression of SNCG mRNA was up-regulated by 13.6-fold and the proliferative activity was higher than that of HepG2 / Neo cells by real-time RT-PCR and Western blotting. 5)%. Overexpression of SNCG decreased the mitotic arrest induced by anti-microtubule drugs in HepG2 / SNCG cells treated with PTX or VCR. The percentage of G2 / M phase in HepG2 / SNCG cells decreased by (19 ± 2.9)% and (27 ± 2.9)% compared with HepG2 / Neo cells ± 1.7)%. The mitotic index of PTX in HepG2 / SNCG, HepG2 / Neo and HepG2 cells were 0.47, 0.64 and 0.67, respectively. The mitotic index of VCR was 0.14, 0.30 and 0.34, respectively. The sensitivity of HepG2 / SNCG cells to PTX and VCR was significantly reduced, and the resistance index was 21 and 15, respectively. The results show that SNCG can significantly reduce its sensitivity to anti-microtubule drugs after hepatoma cell overexpression. SNCG is a potential biomarker for anti-microtubule drug use in hepatocellular carcinoma chemotherapy.