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目的:探讨应用组蛋白脱乙酰酶(his-tone deacetylase,HDAC)抑制剂丙戊酸钠(val-proate acid sodium,VPA)调节组蛋白乙酰化水平对肝细胞性肝癌细胞侵袭、迁移能力的影响及其可能作用机制。方法:采用肿瘤细胞体外迁移实验和Transwell小室体外侵袭模型评价HDAC抑制剂VPA对HepG2细胞浸润转移能力的影响。进一步应用间接免疫荧光技术检测HepG2细胞MMP-2、MMP-9蛋白表达来探讨其作用机制。结果:细胞培养24 h后,对照组迁移细胞数目较多,为(142±16.5)个,而(0.75~4.0)mmol/L VPA试验组细胞迁移数目随药物浓度升高而逐渐由(125±12.4)个减少(42±6.1)个,差异有统计学意义,P<0.001;对照组穿过聚碳酯膜细胞数目(85±7.8)个,明显高于药物实验组(69±6.9~18±3.6)个,差异有统计学意义,P<0.001;与对照组比较,试验组MMP-2、MMP-9蛋白表达被明显下调,并且与肿瘤细胞迁移、侵袭的变化密切相关。结论:应用HDAC抑制剂逆转染色体组蛋白低乙酰化水平可显著抑制肝癌细胞侵袭转移,下调MMP-2和MMP-9表达可能是其发挥作用的主要机制之一。
OBJECTIVE: To investigate the effect of histone acetylation on the invasion and migration of hepatocellular carcinoma cells using histone deacetylase (HDAC) inhibitor val-proate acid sodium (VPA) And its possible mechanism of action. Methods: The invasion and metastasis of HepG2 cells were evaluated by in vitro migration of tumor cells and in vitro invasion assay with Transwell chamber. Indirect immunofluorescence was used to detect the expression of MMP-2 and MMP-9 in HepG2 cells to explore its mechanism. RESULTS: After cultured for 24 h, the number of migrated cells in the control group was (142 ± 16.5) more, while the number of migrated cells in the (0.75 ~ 4.0) mmol / L VPA group gradually increased from (125 ± (42 ± 6.1), P <0.001. The number of cells passing through the polycarbonate membrane in the control group (85 ± 7.8) was significantly higher than that in the drug group (69 ± 6.9 ~ 18) ± 3.6), the difference was statistically significant (P <0.001). Compared with the control group, the expression of MMP-2 and MMP-9 in the experimental group was significantly down-regulated and closely related to the changes of tumor cell migration and invasion. CONCLUSION: HDAC inhibitor reversal of histone hypoacetylation can significantly inhibit the invasion and metastasis of hepatocellular carcinoma cells. Down-regulation of MMP-2 and MMP-9 expression may be one of the main mechanisms.