Icariin Synergizes with Arsenic Trioxide to Suppress Human Hepatocellular Carcinoma

被引:81
作者
Li, Wen [1 ,2 ]
Wang, Min [3 ]
Wang, Lingyun [2 ]
Ji, Shusheng [2 ]
Zhang, Junyong [1 ]
Zhang, Chunqing [1 ]
机构
[1] Shandong Univ, Prov Hosp, Dept Gastroenterol, Jinan 250021, Shandong, Peoples R China
[2] Jining 1 Peoples Hosp, Dept Gastroenterol, Jining 272011, Shandong, Peoples R China
[3] Jining 1 Peoples Hosp, CT Dept, Jining 272011, Shandong, Peoples R China
关键词
Hepatocellular carcinoma; Icariin; Arsenic trioxide; ROS; NF-kappa B; Synergistic effect; FACTOR-KAPPA-B; CANCER-CELLS; INDUCED APOPTOSIS; OXIDATIVE STRESS; GASTRIC-CANCER; BUTHIONINE SULFOXIMINE; ANTITUMOR-ACTIVITY; GROWTH INHIBITION; PROSTATE-CANCER; ACTIVATION;
D O I
10.1007/s12013-013-9724-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Hepatocellular carcinoma (HCC) is an aggressive malignancy with high chemoresistance to chemotherapeutics. Arsenic trioxide (ATO) is of therapeutic potential for the treatment of HCC; however, the therapeutic benefit of ATO is very limited due to narrow therapeutic window. Icariin is a natural compound which inhibits tumour cell growth and induces apoptotic cell death in a variety of cancer cells. This study was designed to determine whether Icariin can potentiate the antitumour activity of ATO in HCC treatment. Cell proliferation and apoptosis were measured using an MTT assay and flow cytometry respectively. Changes in reactive oxygen species (ROS) level and mitochondrial membrane potential were analysed by fluorescence signals. Protein expression was measured by western blotting and NF-kappa B activity was determined by ELISA assay. In addition, the antitumour effect of combination treatment with Icariin and ATO on HCC was evaluated using a murine HCC cancer xenograft model. Icariin inhibited proliferation and induced apoptosis in both of the tested HCC cell lines in a dose-dependent fashion. Icariin enhanced the antitumour activity of ATO both in vitro and in vivo. The antitumour activity of Icariin and its enhancement of the antitumour activity of ATO correlated with the generation of intracellular ROS and inhibition of NF-kappa B activity. Our results showed that Icariin potentiated the antitumour activity of ATO in HCC. Therefore, we propose that the combination treatment with Icariin and ATO might facilitate the optimization of ATO therapy for patients with HCC.
引用
收藏
页码:427 / 436
页数:10
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