Combination of Tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo

被引:90
作者
Zhang, Yuxing [1 ,2 ,5 ]
Wang, Chao [1 ,2 ,5 ]
Wang, Haiwei [1 ,2 ,5 ]
Wang, Kankan [3 ,4 ]
Du, Yanzhi [1 ,2 ]
Zhang, Ji [1 ,2 ,3 ,4 ]
机构
[1] Chinese Acad Sci, SIBS, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hematol, Shanghai 200025, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Sino French Res Ctr Life Sci & Genom, Shanghai 200025, Peoples R China
[5] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China
关键词
Tetrandrine; Cisplatin; Ovarian cancer; Subcutaneous tumor model; Wnt/cadherin; CELL-CYCLE ARREST; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; NEUROBLASTOMA-CELLS; CARCINOMA CELLS; TUMOR-GROWTH; PATHWAY; RECOMMENDATIONS; FANGCHINOLINE; DAUNORUBICIN;
D O I
10.1016/j.canlet.2011.01.022
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Cisplatin, as a first-line drug in the chemotherapy of ovarian cancer, poses significant problems in its toxicity to normal tissue and drug resistance. Here, we report that Tetrandrine, with potent anti-cancer effect, significantly enhances the cytotoxicity of cisplatin in ovarian cancer. The in vitro assay indicates that Tetrandrine can markedly increase growth suppression and apoptosis induced by cisplatin and cause redistribution of the cell cycle. Further assay indicates that modulation of Wnt/cadherin signaling pathway contributes to the chemosensitizing effect of Tetrandrine on the cytotoxicity of cisplatin in ovarian cancer. In vivo, the combination of Tetrandrine and cisplatin exhibits the strongest anti-cancer effect compared with each drug alone, with no obvious additional toxicity. These results provide rational evidence supporting the application of Tetrandrine as an adjunct to cis-plann in improvement of chemotherapy in ovarian cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:21 / 32
页数:12
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