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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 detect the cytotoxic effect of dipyridamole on tumor cells and to observe the changes of the morphology of the tumor cells after drug treatment. The mechanism of action of the drug on the cell cycle and apoptosis was explored. Methods K562 human chronic myeloid leukemia cells, MCF-7 human breast cancer cells, A549 human lung cancer cells and BEL-7402 human hepatocellular carcinoma cells were treated with neutral red assay. The half inhibitory concentration (IC50), optical microscope The morphology of the cells after the drug was observed, and the cell cycle phase and apoptosis rate were determined by flow cytometry. Results Dipyridamole significantly inhibited the growth of all four tumor cells and had a good dose-response relationship. Compared with the control group, the number of BEL-7402 cells decreased significantly, the distribution was sparse, the morphology became longer, the cell protrusion became longer and the number of round cells increased. The effect of 40 and 60μg / ml dipyridamole on BEL-7402 cells for 2 days increased the number of G0 / G1 phase cells (P <0.01). The number of cells in BEL-7402 cells treated with 60μg / ml dipyridamole for 2 days significantly increased (P <0.01) and the apoptosis rate was 10.58%. Conclusions Dipyridamole can inhibit the growth of tumor cells and change the morphology of BEL-7402 cells. Meanwhile, the cell cycle arrest of BEL-7402 can be arrested in G0 / G1 phase and high dose of dipyridamole Mo-induced apoptosis in BEL-7402 cells.