【摘要】 目的:探讨苦马豆素（swainsonine,SW）体外诱导人胃癌细胞株SGC-7901凋亡的机制。方法:应用MTT法确定SW对体外培养的SGC-7901细胞的作用浓度;通过流式细胞术及凋亡相关调控基因p53,c-myc,Bcl-2的检测对细胞凋亡及细胞周期的测定,观察SW对胃癌细胞SGC-7901增殖周期的影响以及抑制肿瘤细胞增殖的方式;同时利用激光共聚焦显微镜监测细胞内Ca²⁺浓度,研究SW与细胞内Ca²⁺超载的关系。结果:SW体外抗SGC-7901细胞的完全致死浓度为6．2μg·mL^-1,高于0．05μg·mL^-1时抑制作用明显（P＜0．05）,其IC₅₀为0．84μg·mL～（-1）;经SW 0．5,1．5,4．5μg·mL^-1处理24h可引起凋亡抑制基因p53和Bcl-2的明显下降,凋亡促进基因c-myc明显升高以及肿瘤细胞内Ca²⁺超载,最终诱导SGC-7901细胞凋亡。实验还证实SW主要作用于肿瘤细胞的S期,使瘤细胞主要积聚在S期。结论:SW通过多种途径诱导细胞凋亡可能是其发挥抗癌作用的重要机制。更多还原

【Abstract】 Objective:To investigate the apoptotic mechanism of the human gastric carcinoma cell SGC-7901 in vitro by swainsonine.Methods:After the cultures of the cell SGC-7901 with a series of concentrations of swainsonine,the ratio of dose-inhibition (IC₅₀) of swainsonine to the cell SGC-7901 were examined by MTT assay.The cell cycle distribution and apoptotic rates were analyzed by flow ey- tometry.Expression of p53,c-myc and Bcl-2 was assayed using an immunoeytochemical method.The concentration of intracellular calcium ([Ca²⁺]_i) was measured by laser scanning confocal microscope （LSCM）.Results:Swainsonine at the concentration 0.05μg·mL^-1 or up significantly inhibited the cell growth of SGC-7901 in vitro with an IC₅₀0.84μg·mL^-1 and at 6.2μg·mL^-1 resulted to the apoptosis of the cell.At the concentrations of 0.5,1.5 and 4.5μg·mL^-1,swainsonine decreased the expression of apoptosis-inhibited gene p53 and Bcl-2,increased the apoptosis-triggered gene c-myc,and overloading of [Ca²⁺]_i inside of the cell post the 24-hours culture leading to the apoptosis of the cell SGC-7901.More- over,swainsonine was a S phase-specific cytotoxic agent against the cell SGC-7901.Conclusion:Swain- sonine is effective against carcinoma by several apoptotic mechanisms.更多还原