新型微管抑制剂Yf9b能够诱导Hela细胞G2/M期阻滞和凋亡

Yf9b,a novel microtubule inhibitor,induced G2/M phase arrest and apoptosis in Hela cells

目的考察新型微管抑制剂2-甲氧基-5-(4-(3,4,5-三家氧基苯基)-1,3-硒唑-5-基)苯胺[2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1,3-selenazol-5-yl)aniline,Yf9b]对多种人源性肿瘤细胞的抗肿瘤活性,并研究Yf9b抑制人宫颈癌Hela细胞增殖的机制。方法采用MTT法考察Yf9b对多种肿瘤细胞的增殖抑制作用。免疫荧光染色观察Yf9b与康普瑞丁(combretastatin A-4,CA-4)对微管的抑制作用。流式细胞技术考察Yf9b与CA-4对Hela细胞周期的影响,并考察Yf9b诱导Hela细胞凋亡的情况。结果 Yf9b的作用时间与剂量依赖性地抑制Hela细胞增殖,半数抑制浓度(IC50)为(42.9±2.7)nmol·L-1。Yf9b同母体化合物CA-4一样能抑制微管聚合,将Hela细胞阻滞在G2/M期,并最终诱导细胞凋亡。结论 Yf9b是一种新型微管抑制剂,能够诱导Hela细胞G2/M期阻滞和凋亡。

Objective In this study, we intended to investigate the antitumor activity of Yf9b on different human cancer cell lines, and to study the mechanism of its cytotoxic upon Hela cells. Methods MTT assay was used to detect the cytotoxic effect of Yf9b on different human cancer cell lines. Immunofluorescence staining was used to observe the change of mierotubule in Hela cells after treated with Yf9b and combretastatin （CA-4）. Flow cytometry was applied to observe the change of cell cycle and apoptosis rate in Yf9b or CA-4 treated Hela cells. Results MTT assay showed that Yf9b exhibited time-and dose-dependent cell-killing effect on Hela cells, and the ICs0 value of Yf9b for Hela cells was （42.9 ± 2.7 ） nmol- L1. Cell cycle analysis revealed that Yf9b treatment resulted in cell cycle arrest at the G2/M phase in a time- dependentmanner with subsequent apoptosis induction. Conclusions Yf9b exhibits antitumor activity via the mechanism of disrupting the microtubule assembly, causingcell cycle arrest and consequently inducing apoptosis in Hela cells.