机构：[1]Department of Obstetrics and Gynecology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou 450003, Henan, China[2]State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院[3]Medical Genetics Institute of Henan Province, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Polo-like kinase 4 (PLK4), a member of the polo-like kinase family, plays several important roles in mitotic regulation, including centrosome duplication, spindle formation, and cytokinesis. PLK4 overexpression is frequently detected in many human cancers, including ovarian cancer, and the inhibition of PLK4 activity results in cancer cell mitotic arrest and apoptosis. Therefore, PLK4 might be a valid therapeutic target for antitumor therapy. In the present study, we aimed to determine if YLZ-F5, a potent small-molecule inhibitor of PLK4, inhibits ovarian cancer cell growth.
MTT assay showed that YLZ-F5 inhibited ovarian cancer cell proliferation in a concentration- and time-dependent manner. The results of colony formation assays were consistent with those of the MTT assay results. In addition, YLZ-F5 induced ovarian cancer cell apoptosis that was associated with activation of caspase-3/caspase-9. Moreover, YLZ-F5 caused aberrant in centriole duplication that was associated with the inhibition of PLK4 phosphorylation. Notably, we showed that YLZ-F5 promoted the accumulation of ovarian cancer cells with mitotic defects (> 4 N DNA content) in a concentration-dependent manner. Furthermore, YLZ-F5 markedly inhibited the migration of A2780 cells.
Taken together, these findings suggest that YLZ-F5 is a potential drug candidate for human ovarian cancer.
基金：
This research was supported by the China Postdoctoral Science Foundation [Grant number 2019M652543] and
Sichuan Provincial Science and technology program for Key research
and development, China (No. 2018SZ0007).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|3 区医学
小类|3 区药学4 区肿瘤学
最新[2023]版：
大类|4 区医学
小类|3 区药学4 区肿瘤学
第一作者：
第一作者机构：[1]Department of Obstetrics and Gynecology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou 450003, Henan, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhu Yongxia,Liu Zhihao,Qu Yanling,et al.YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.[J].Cancer chemotherapy and pharmacology.2020,86(1):33-43.doi:10.1007/s00280-020-04098-w.
APA：
Zhu Yongxia,Liu Zhihao,Qu Yanling,Zeng Jun,Yang Meiqin...&Wang Yue.(2020).YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects..Cancer chemotherapy and pharmacology,86,(1)
MLA：
Zhu Yongxia,et al."YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.".Cancer chemotherapy and pharmacology 86..1(2020):33-43
