芹菜素
细胞凋亡
碘化丙啶
化学
活性氧
膜联蛋白
细胞毒性
药理学
体内
癌症研究
聚ADP核糖聚合酶
分子生物学
生物化学
体外
程序性细胞死亡
生物
聚合酶
抗氧化剂
类黄酮
生物技术
基因
作者
Xiao Hu,Jiyun Liang,Xue‐Jun Guo,Li Liu,Yabing Guo
标识
DOI:10.1111/1440-1681.12333
摘要
Summary The development of chemoresistance may reduce the efficacy of chemotherapeutic drugs for treating hepatocellular carcinoma (HCC). In the present study, the effects of apigenin on intensifying the chemosensitivity of HCC cells and an HCC xenograft model in response to 5‐fluorouracil (5‐FU) were investigated. Sub‐toxic concentrations of apigenin (4 μ mol/L) significantly enhanced the cytotoxicity of 5‐FU (100 μ g/mL) in HCC cells. In vivo , combined treatment with apigenin (20 mg/kg, five times/week for 3 weeks) and 5‐FU (20 mg/kg for 5 consecutive days) significantly inhibited the growth of HCC xenograft tumours. Annexin V–propidium iodide dual staining assays, terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling assays and western blotting analysis were used to confirm the synergistic effects of apigenin and 5‐FU on HCC apoptosis. Coincubation of HCC cells with apigenin and 5‐FU increased levels of reactive oxygen species (ROS), which was followed by a decrease in the mitochondrial membrane potential (ΔΨm). In addition, combined triggered the mitochondrial apoptotic pathway, as indicated by decreased Bcl‐2 expression and loss of ΔΨm, with significant activation of caspase 3 and poly(ADP‐ribose) polymerase. The present study is the first to demonstrate that apigenin may potentiate the cytotoxicity of 5‐FU in HCC via inhibition of ROS‐mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
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