呫吨酮并吡啶衍生物XP-15联合紫杉醇对耐药肝癌细胞QGY-7701的体外抑制作用

目的:探索呫吨酮并吡啶衍生物XP-15联合紫杉醇对人肝癌QGY-7701耐药细胞株的体外抗肿瘤作用。方法:运用CCK8法、Transwell实验和流式细胞仪检测凋亡技术观察细胞功能学变化,运用Western Blot蛋白免疫印迹技术探索其可能的作用机制。结果:XP-15可明显增强紫杉醇对耐药QGY-7701细胞的抑制作用,XP-15联合紫杉醇作用于耐药QGY-7701细胞24 h后,QGY-7701细胞活力明显减弱,且其侵袭迁移能力明显降低,同时流式细胞仪凋亡检测提示细胞凋亡百分比明显增加。Western Blot蛋白免疫印迹亦证实细胞抗凋亡蛋白bcl-2表达明显降低,肝癌增殖分化相关PI3K及AKT蛋白分子表达减少。结论:XP-15具有增敏紫杉醇诱导耐药QGY-7701细胞凋亡同时抑制其增殖活力的作用,其作用机制可能与下调PI3K-AKT通路活性,同时减少bcl-2抑制凋亡蛋白表达相关。

Inhibitory effect of XP-15 combined with taxinol on drug-resistant hepatocellular carcinoma cell line QGY-7701 in vitro

Objective:To observe the antiproliferative effect of a new xanthono-pyridine derivative(XP-15) combined with taxinol on human hepatocellular carcinoma QGY-7701，which with multi-drug resistance.Methods:CCK8 assay，Transwell experiment and flow cytometry were applied to observe the change of cell function.Western Blot were employed to investigate its possible action mechanism.Results:The results showed that XP-15 enhance the antiproliferative ability of taxinol to QGY-7701，also the combination reduced metastasis of the cell and promoted the apoptosis.Through Western Blot we found out that the level of anti-apoptosis protein bcl-2 were down-regulated and the expression of PI3K and AKT protein which closely related with proliferation and differentiation of liver cancer were reduced too.Conclusion:We concluded that XP-15 probably sensitize the antitumor effect of taxinol to QGY-7701 through depressing the PI3K-AKT pathway.