BBI608对肝癌细胞HepG2的抑制作用及其机理研究

Inhibitory effect and mechanism of BBI608 on hepatocellular carcinoma

目的研究STAT3抑制剂BBI608对肝癌细胞的抑制作用及其机理。方法以不同浓度的BBI608作用于对数生长期的肝癌细胞HepG2,应用CCK8法检测细胞增殖,Annexin V-FITC/PI双染检测细胞凋亡,Western blot方法检测p-STAT3及凋亡相关蛋白Bcl-2和Bax的表达。结果 BBI608作用于HepG2细胞活细胞数显著减少,呈浓度和时间依赖性,在BBI60830μM作用于肝癌细胞12 h,凋亡率显著升高。BBI608呈剂量依赖性地降低肝癌细胞中p-STAT3及凋亡相关蛋白Bcl-2的表达和上调Bax蛋白的表达。结论 BBI608抑制肝癌细胞的增殖发挥抗肝癌作用与抑制STAT3的磷酸化,下调Bcl-2的表达和上调Bax的表达相关。

Objective To investigate the effects of STAT3 inhibitor BBI608 on human hepatocellular carcinoma in vitro. Methods HepG2 cells were treated with different concentrations of BBI608. The inhibitory rate of cell proliferation was measured by CCK8 assay. Apoptosis was detected by flow cytometry. Western blot was used to detect the expressions of p-STAT3 and apoptosis related proteins Bcl-2 and Bax. Results The proliferation of HepG2 cells was inhibited by BBI608 in a dose and time dependent manner, and BBI608 induced apoptosis of HepG2 cells in a dose dependent manner. BBI608 downregulated the expression of p-STAT3 and Bcl-2 and upregulated the expression of Bax. Conclusion The inhibitory effect of BBI608 on hepatocellular carcinoma is related to the inhibition of STAT3 phosphorylation and Bcl-2 expression, and increasing the Bax expression.