GPI-PLD通过下调PI3K-Akt信号通路活性抑制肝癌细胞的生长

GPI-PLD inhibits the growth of hepatoma cells by downregulation of PI3K-Akt signaling pathway

目的:明确糖基化磷脂酰肌醇特异性磷酯酶D(glycosylphosphatidylinositol-specific phospholipase D,GPIPLD)对肝癌细胞HepG2的影响以及可能的调控分子机制。方法:通过转染构建高表达GPI-PLD模型,利用M、荧光染色以及Western印迹检测高表达GPI-PLD对肝癌细胞的影响,同时接种于裸鼠模型中,进一步明确GPI-PLD在体内对肝癌细胞的影响。结果:与空白组和对照组相比,GPI-PLD组PI3K-Akt信号通路活性明显受到抑制,肝癌细胞增殖活性明显受到抑制并呈现典型的凋亡形态。肝癌裸鼠模型结果显示GPI-PLD组肿瘤的生长速度、肿瘤质量[(1.87±0.09)g]小于空白组[(2.20±0.17)g]和对照组[(2.15±0.09)g],GPI-PLD组AST,ALT,AFP血清浓度显著低于空白组和对照组(P<0.05)。结论:GPI-PLD可通过下调PI3K-Akt信号通路活性,抑制肝癌细胞的增殖及体内生长,促进肝癌细胞的凋亡。

Objective: To clarify the effect of glycosylphosphatidylinositol-specific phospholipase D(GPIPLD) on hepatoma cells HepG2 and the possible molecular mechanism.Methods: MTT, fluorescent staining and Western blot were applied to analyze the effect and molecular mechanism of GPI-PLD on hepatoma cells by transfected high expression GPI-PLD model. We inoculated HepG2 in nude mice models to further clarify the effect of GPI-PLD on hepatoma cells in vivo.Results: Compared with the control groups, PI3K-Akt signaling pathway activity and proliferation of hepatoma cells were significantly inhibited in the GPI-PLD group. Nude mice models showed that the tumor growth and tumor weight [(1.87±0.09) g] of the GPI-PLD group were significantly less than those of the blank control group [(2.20 ± 0.17) g] and the negative control group [(2.15± 0.09) g]. AST, ALT and AFP serum concentration in the GPI-PLD group were significantly lower than those of the control groups(P<0.05). Conclusion: GPI-PLD can inhibit the proliferation of hepatoma cells and growth in vivo, and promote the apoptosis of hepatoma cells by reducing the activity of PI3K-Akt signaling pathway.