标题:Synergistic Inhibition of Breast Cancer Cell Growth by an Epigenome-Targeting Drug and a Tyrosine Kinase Inhibitor
作者:Wu, Yu Shan; Quan, Yuan; Zhang, Dong Xing; Liu, Dong Wu; Zhang, Xiu Zhen
作者机构:[Wu, Yu Shan; Zhang, Dong Xing; Liu, Dong Wu; Zhang, Xiu Zhen] Shandong Univ Technol, Sch Life Sci, Zibo 255049, Peoples R China.; [Quan, Yuan] Huaz 更多
通讯作者:Zhang, XZ
通讯作者地址:[Zhang, XZ]Shandong Univ Technol, Sch Life Sci, Zibo 255049, Peoples R China.
来源:BIOLOGICAL & PHARMACEUTICAL BULLETIN
出版年:2017
卷:40
期:10
页码:1747-1753
DOI:10.1248/bpb.b17-00360
关键词:vorinostat; dasatinib; breast cancer; apoptosis; combination therapy
摘要:Background: Epigenome-targeting drugs, for example, histone decetylases (HDACs) inhibitors, have been recently shown to induce apoptosis in a variety of cancer cells, which could potentially be used as anticancer therapy. Tyrosine kinase inhibitors (TKIs) have been widely used in clinical trials of various cancers. HDAC inhibitor vorinostat, TKIs dasatinib have been tested in pivotal phase 2 clinical trials in patients with breast cancer. The combination treatment of vorinostat with dasatinib is expected to have synergistic effect on inhibiting breast cancer cell growth. Materials and Methods: Antiproliferation effects of the combined drugs on MCF-7 cells were designed according to Chou Talalay method and analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell-cycle perturbation and cell apoptosis induction of the combination drugs were examined by Flow cytometry. The generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and the expression of Bcl-2 were determined by Western blot. Results: Our results revealed that the combination treatment had synergistic effects on anti-MCF7 cells, enhanced G(2)/M cell arrest, the generation of ROS, the loss of mitochondrial membrane potential, and cell apoptosis in MCF-7 cells in synergy. Moreover, the combination treatment decreased Bc1-2 expression. Conclusion: Our results demonstrated that the combination of vorinostat with dasatinib exerted synergistic anticancer effects on MCF-7 cells by inducing cell cycle arrest, ROS production, and apoptosis through the mitochondria-mediated intrinsic pathway.
收录类别:SCIE
WOS核心被引频次:2
资源类型:期刊论文
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