Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2017-12-02 , DOI: 10.1016/j.cbi.2017.11.020 Ai-Mei Gao , Xiao-Yu Zhang , Juan-Ni Hu , Zun-Ping Ke
Chemo-resistance is a serious obstacle for successful treatment of cancer. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various malignant cancers. This study aimed to investigate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7-dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR-520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b. Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma.
中文翻译:
芹菜素通过调节miR-520b / ATG7轴使肝癌细胞对阿霉素敏感
耐化学性是成功治疗癌症的严重障碍。芹菜素是一种饮食性黄酮类化合物,据报道可作为多种恶性肿瘤的抗癌药物。这项研究旨在探讨芹菜素在抗阿霉素的肝癌细胞系BEL-7402 / ADM中的潜在化学增敏作用。我们观察到芹菜素在BEL-7402 / ADM细胞中显着增强了阿霉素的敏感性,诱导了miR-520b的表达并抑制了ATG7依赖性自噬。此外,我们还显示miR-520b模拟物增加了阿霉素的敏感性并抑制了ATG7依赖性自噬。同时,我们表明ATG7是miR-520b的潜在靶标。此外,APG通过上调miR-520b和抑制ATG7抑制裸鼠肝细胞癌异种移植物的生长。