三氧化二砷诱导肠癌HT-29细胞周期阻滞及凋亡的研究

Cell cycle arrest and apoptosis induced by arsenic trioxide in colorectal cancer cell line HT-29

目的:探讨三氧化二砷(As2O3)对结肠癌细胞增殖的抑制作用及对细胞周期和凋亡的影响。方法:采用MTT法测定细胞增殖活力,通过细胞形态学观察细胞分裂及凋亡,应用流式细胞仪进行细胞周期解析、凋亡的检测。结果:As2O3呈剂量-时间依赖性抑制结肠癌HT-29细胞系的增殖,作用24、48及72 h后抑制50%细胞生长的药物浓度(IC50)分别为40.03,13.76,4.53μmol/L,与对照组差异显著(P<0.05)。2μmol/L与5μmol/L的As2O3作用24 h后,细胞周期出现G2/M期阻滞及亚二倍体凋亡峰,随着作用时间的延长,凋亡细胞随G2/M期细胞减少而逐渐增多。细胞形态学观察分裂期细胞及凋亡细胞明显增加。结论:As2O3抑制结肠癌HT-29细胞的增殖,诱导G2/M期阻滞及细胞凋亡。

Objective： To study the effect of arsenic trioxide（As2O3）on the cell proliferation,cell cycle,and cell apoptosis in colorectal cancer cell line HT-29. Methods： The cell proliferation and the cell cycle and apoptosis of HT-29 cells were determined by MTY assay and flow cytometry, respectively, The morphological changes of HT-29 cells were observed under light microscope. Results： As：03 inhibited the proliferation of HT-29 cells in a dose-and time-dependent manner, and the 50% inhibitory concentrations （IC50）were 40.03,13.76, and 4.53 μmol/L 24,48,and 72 hours after the administration of As2O3,respectively. GriM phase arrest and cell apoptosis were induced by As2O3,and sub-G0G1 phase cells increased with the decrease of GriM phase cells 24 hours after the administration of As2O3. Thee number of mitotic and apoptotic cells increased 12 to 72 hours after the administration of 0.5 to 5 μmol/L of As2O3. Conclusion： As2O3 could inhibit the proliferation of colorectal cancer cell line HT-29 and induce GriM phase arrest and cell apoptesis.