醋酸甲地孕酮联合三氧化二砷对肝癌HepG2细胞株体外抑制作用的研究

The effect of megestrol acetate in combination with arsenic trioxide on growth of HepG 2 cells

目的探讨醋酸甲地孕酮(MA)联合三氧化二砷(As2O3)对肝癌Hep G2细胞株体外增殖的影响及其可能机制。方法将对数生长期Hep G2细胞分为4组:MA单药组、As2O3单药组、MA+As2O3联合组和对照组,根据前期研究结果确定药物剂量分别为75.0μmol/L MA、1.0μg/ml As2O3,对照组加入等量细胞培养液。24 h后采用CCK-8方法、流式细胞学检测及Western blotting检测MA单药组、As2O3单药组及MA+As2O3联合组对Hep G2细胞增殖、细胞凋亡及X连锁凋亡抑制蛋白(XIAP)表达的影响。结果 CCK-8法显示MA+As2O3组较MA或As2O3单药组均能够明显抑制Hep G2细胞生长;流式细胞仪结果显示MA+As2O3联合组的细胞凋亡率高于MA或As2O3单药组。MA+As2O3作用后XIAP表达较MA或As2O3单药组降低。结论 MA联合As2O3能够发挥对Hep G2细胞协同抑制作用,其中诱导细胞凋亡可能是其机制之一。

Objective To investigated the anti-tumor effects of megestrol acetate （MA） in combination with arsenic trioxide （ As2O3 ） in hepatocellular carcinoma （HCC）. Methods The HepG2 cells were divided into 4 groups ： treated with MA （ 75 μmol/L） alone, As2O3（ 1.0 μg/ml）alone, or MA （75μmol/L） in combination with As2O3 （ 1.0 μg/ml）and negative control group for 24 h. The doses of the drugs were confirmed according to our previous researches. The effect of MA combined with As2O3 on HepG2 cell growth was detected by Cell Counting Kit method （CCK-8） and flow cytometry assay. The expressive effect of X-linked inhibitor of ap- optosis protein（XIAP） in HepG2 cells was analyzed with Western blotting. Results CCK-8 assay showed MA combined with As2O3 could significantly inhibit the growth of HepG2 cells compared with MA or As2O3 alone. The apoptotic rate of MA combined with As2O3 group was significantly higher than those of MA or As2O3 group. Compared with MA or As2O3 group, MA combined with As2O3 signifi- cantly decreased the expression of apoptosis-related proteins XIAP. Conclusion MA combined with As2O3 could promote inhibition effect of HepG2 cells, inducing apoptosis may be one of the mechanisms.