阿苯达唑对人胃癌细胞株MKN-45体外生长及细胞周期的影响

Effects of albendazole on the proliferation and cell cycle of human gastric cancer MKN- 45 cells in vitro

目的探讨抗寄生虫药物阿苯达唑（ABZ）对人胃癌细胞株MKN-45体外生长及细胞周期的影响，并分析其对细胞周期产生阻滞作用的可能机制。方法CCK-8法检测不同浓度ABZ作用不同时间对MKN-45细胞增殖能力的影响，并计算增殖抑制率及半数抑制浓度（IC50）。PI染色流式细胞术分析细胞周期，免疫荧光法观察药物处理前后的MKN-45细胞形态及微管结构的变化。结果与对照组比较，ABZ处理组MKN-45细胞的增殖受到明显抑制，该作用呈剂量和时间依赖性（P〈0．05），24、48、72、96h的IC50值分别为0．756、0．429、0．350、0．309μmoL／L。ABZ作用于MKN-45细胞24h后，在0．25～1．0μmol／L范围内以浓度依赖性方式诱导MKN-45细胞周期阻滞于G2／M期（P〈0．05）。经0．5μmol／L阿苯达唑处理后的MKN-45细胞出现对照组少有的多核及细胞轮廓不规则等改变，而对照组细胞形态正常，微管结构清晰完整。结论阿苯达唑能通过影响胃癌细胞微管蛋白功能使细胞周期阻滞于M期，从而抑制胃癌细胞的增殖。

Objective To investigate the effects of albendazole （ABZ） on the proliferation and cell cycle of human gastric cancer MKN -45 cells and possible mechanisms involved. Methods The proliferation of MKN -45 ceils exposed to different concentrations of ABZ for various periods of time was examined by the cell counting kit - 8 （ CCK - 8 ） , resulting in the rate of inhibition and the half maximal inhibitory concentration （ IC50 ）. The cell cycle was detected by propidium iodide staining for fluorescence - activated ceil sorting （FACS）. The morphological changes and structural changes of microtubules before and after administration of ABZ were determined by immunofluoreseenee. Results pared with the control, ABZ treatment could remarkably inhibit the proliferation of gastric carcinoma MKN - 45 ceils in a dose - and time - dependent manner （ P 〈 0. 05 ）. The value of IC50 was 0. 756 μmol/L for 24 h, 0.429 μmoL/L for 48 h, 0. 350 μmol/L for 72 h and 0. 309 μmol/L for 96 h. After exposure to 0.25 - 1.0 μmol/L of ABZ for 24 hours, MKN-45 cells were retarded at G2/M phase in a dose -dependent manner （P 〈 0.05）. The cells treated with 0.5 μmol/L of ABZ became muhinucleate, while irregular cell outline and other changes appeared that were rarely seen in the control. Conclusion Albendazole can inhibit the proliferation of gastric cancer MKN -45 cells through inducing G2/M phase arrest and then resulting in the dysfunction of tubulin.