目的: 探讨地西他滨（decitabine,DAC）对肝癌细胞迁移和侵袭的作用及分子机制。方法: MTT法检测不同浓度DAC对肝癌MHCC97H细胞活力的影响;采用细胞划痕愈合和Transwell侵袭实验测定不同浓度DAC对肝癌MHCC97H细胞迁移和侵袭能力的影响;DAC对肝癌细胞（MHCC97H和SK-Hep-1）细胞因子信号传导抑制因子1（suppressor of cytokine signaling 1,SOCS1）蛋白表达量的影响采用WB检测;siRNA转染实验敲低肝癌MHCC97H细胞SOCS1表达,观察细胞迁移和侵袭能力变化。结果: DAC呈浓度依赖的方式抑制肝癌MHCC97H细胞活力（IC50值为5.0 μM）,且对细胞迁移和侵袭具有抑制作用。敲低SOCS1表达后,肝癌MHCC97H细胞的迁移和侵袭增强。DAC能上调肝癌细胞MHCC97H和SK-Hep-1的SOCS1表达,且呈浓度依赖性。DAC能逆转低表达SOCS1对肝癌MHCC97H细胞迁移和侵袭的促进作用。结论: DAC通过上调SOCS1表达抑制肝癌细胞的迁移和侵袭。
Abstract
Objective This study was designed to investigate the effect of Decitabine (DAC) on hepatocellular carcinoma cell migration and invasion and to explore its molecular mechanisms. Methods MTT assay was used to detect the effect of different concentrations of DAC on the viability of hepatocellular carcinoma MHCC97H cells. The influence of different concentrations of DAC on the migratory and invasive abilities of hepatocellular carcinoma MHCC97H cells were determined by cell wound healing and transwell invasion assays. The impact of DAC on the protein expression of suppressor of cytokine signaling 1(SOCS1) in hepatocellular carcinoma MHCC97H and SK-Hep-1 cells was assessed by Western blot (WB). The siRNA transfection assay was performed to knock down the expression of SOCS1 in hepatocellular carcinoma MHCC97H cells, and changes in the migratory and invasive ability of cells were observed. Results DAC inhibited the viability of hepatocellular carcinoma MHCC97H cells in a concentration-dependent manner (IC50=5.0 μM) and had the inhibitory effect on cell migration and invasion. Knocking down the expression of SOCS1 enhanced the migration and invasion of hepatocellular carcinoma MHCC97H cells. DAC upregulated the expression of SOCS1 in hepatocellular carcinoma cells (MHCC97H and SK-Hep-1) in a concentration-dependent manner, and DAC reversed the promotion of migration and invasion of hepatocellular carcinoma MHCC97H cells by low expression of SOCS1. Conclusion DAC inhibits migration and invasion of hepatocellular carcinoma cells by upregulating SOCS1 expression.
关键词
地西他滨 /
细胞因子信号传导抑制因子1 /
肝癌细胞 /
迁移 /
侵袭
Key words
decitabine /
suppressor of cytokine signaling 1(SOCS1) /
hepatocellular carcinoma cells /
migration /
invasion
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基金
湖南省自然科学基金面上项目“CAS调控DNMT1/SOCS1信号轴抑制肝癌干样细胞干性特征的机制研究”（2021JJ30462）
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