Wang Bo-Yong, Liu Quan-Yan, Cao Jun, Chen Ji-Wei, Liu Zhi-Su
Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Drug Des Devel Ther. 2016 Mar 16;10:1181-9. doi: 10.2147/DDDT.S86317. eCollection 2016.
Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24-72 hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC.
细胞周期蛋白依赖性激酶（CDK）家族成员被认为是癌症有吸引力的治疗靶点。在本研究中，我们旨在研究选择性CDK7抑制剂BS-181对胃癌（GC）细胞系的抗癌作用。人GC细胞（BGC823）在不同浓度的BS-181存在或不存在的情况下培养24至72小时。BS-181显著降低了GC细胞中CDK7的活性，同时下调了细胞周期蛋白D1和XIAP。用BS-181处理诱导细胞周期停滞和凋亡。在用BS-181处理的细胞中，Bax和caspase-3的表达显著增加，而Bcl-2表达降低。此外，用BS-181抑制CDK7导致胃细胞的增殖、迁移和侵袭率降低。这些结果证明了选择性CDK7抑制剂BS-181在BGC823细胞中的抗癌活性，表明CDK7可能作为GC治疗的新靶点。
