DEHP诱导人肝癌HuH-7细胞增殖迁移及二甲双胍对其抑制作用

Human Hepatoma HuH-7 Cells Proliferation and Migration Induced by DEHP and Its Inhibition by Metformin

目的研究邻苯二甲酸二(2-乙基己基)酯(DEHP)诱导人肝癌细胞HuH-7增殖迁移作用及二甲双胍对其抑制作用。方法镜下观察细胞形态变化,MTT细胞活性测定法检测DEHP诱导的增殖作用,二甲双胍、PI3K抑制剂(LY294002)的抑制作用。通过划痕—修复实验和Transwell迁移实验观察DEHP诱导HuH-7细胞的迁移作用及二甲双胍、LY294002的抑制作用。结果浓度为40和80μg/mL的DEHP可以显著促进HuH-7细胞增殖,与对照组相比差异具有统计学意义(P<0.05),该增殖作用可被浓度为10 mg/mL的二甲双胍、浓度为50μmol/L的LY294002抑制(P<0.05)。划痕—修复实验和Transwell实验证明DEHP可以诱导HuH-7细胞迁移(P<0.05),该作用可被二甲双胍、LY294002抑制(P<0.05)。结论 DEHP可以促进人肝癌细胞HuH-7增殖与迁移,二甲双胍可以抑制该增殖迁移作用,从而起到保护作用。

Objective To explore the role of bis(2-ethylhexyl) phthalate(DEHP) in inducing the proliferation and migration of human hepatoma HuH-7 cells and metformin inhibitory effect. Methods Cell morphology-based observation and MTT assay(for assessing cellular activity) were used to determine DEHP-induced proliferation and the inhibitory effect of metformin and phosphatidylinositol 3-kinase(PI3 K) inhibitor(LY294002). The wound healing assay and Transwell migration assay were used to assess DEHP-induced migration of HuH-7 cells and the inhibitory effect of metformin and LY294002. Results DEHP at 40 and 80 μg/mL significantly promoted the proliferation of HuH-7 cells as compared with that in control group(P <0.05);and the proliferation was inhibited by metformin at 10 mg/mL and LY294002 at 50 μmol/L(P <0.05). The wound healing assay and Transwell migration assay proved that DEHP induced HuH-7 cell migration(P <0.05), which was inhibited by metformin and LY294002(P <0.05). Conclusion DEHP can promote the proliferation and migration of human hepatoma HuH-7 cells;metformin can inhibit the proliferation and migration, and therefore plays a protective role.