摘要
目的检测双嘧达莫对肿瘤细胞的细胞毒作用,观察药物作用后肿瘤细胞形态的变化,通过测定药物对细胞周期及细胞凋亡的影响探讨其作用机制。方法用中性红法对K562人慢性髓原白血病细胞、MCF-7人乳腺癌细胞、A549人肺癌细胞和BEL-7402人肝癌细胞4种细胞进行细胞毒实验,计算半数抑制浓度IC50,光学显微镜下观察药物作用后的细胞形态,采用流式细胞术测定细胞周期时相和细胞凋亡率。结果双嘧达莫对四种肿瘤细胞的生长均有明显的抑制作用,且有较好的剂量-效应关系。药物作用2d后,与对照组相比,BEL-7402细胞数量明显减少,分布稀疏,形态变长,细胞突起变长,圆形细胞增多。40和60μg/ml双嘧达莫作用于BEL-7402细胞2d,可使G0/G1期细胞增多(P<0.01)。60μg/ml双嘧达莫作用2d可以使BEL-7402细胞处于凋亡早期和凋亡晚期的细胞数量明显增加(P<0.01),凋亡率为10.58%。结论双嘧达莫具有抑制肿瘤细胞生长的作用,使BEL-7402细胞形态发生改变,同时半数抑制浓度以上的剂量可将BEL-7402细胞周期阻滞在G0/G1期,高剂量的双嘧达莫对BEL-7402细胞凋亡具有诱导作用。
Objective To investigate the toxic effect of Dipyridamole on cancer cells and the influence on cell cycle and apoptosis. Methods The growth inhibition effect of dipyridamole on K562 human chronic myelogenous leukaemia cells,MCF-7 human breast cancer cells,A549 human lung cancer cells and BEL-7402 human hepatoma cells were tested separately by Neutral Red Staining method. The cell cycle phase and apoptosis rate of BEL-7402 cells were studied by flow cytometry analysis. Results The data showed that Dipyridamole inhibited the cell growth of the four kinds of cells with good dose-effect relationship. It was found under optical microscope that the BEL-7402 cell number of exposed group is obviously reduced and cells presented diverse shape in different doses. Compared with control group,the Dipyridamole in dose of 40μg /ml and 60μg /ml increased BEL-7402 cells in G0 /G1 phase(P 0. 01) after 2d’s exposure. Meanwhile,in the apoptosis investigation,Dipyridamole in the dose of 60μg /ml obviously increased the number of apoptosis cells( P 0. 01) in the rate of 10. 58% . Conclusion Dipyridamole has inhibition effect on carcinoma cells indeed,and in the dose above IC50 ,it will block cell growth in G0 /G1 phase and induce apoptosis of BEL-7402 cells.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2010年第3期186-189,共4页
Journal of Toxicology