硫化砷对白血病细胞的生长抑制及作用机制

 目的 研究硫化砷（As4S4）通过体外培养对白血病细胞HL-60细胞的生长抑制作用及其分子机制。方法 以不同浓度（7.5 ~ 60 mmol／L）的As4S4作用于体外培养HL-60细胞12 ~ 48 h，四甲基偶氮唑蓝（MTT）法检测细胞生长抑制率,流式细胞仪观察细胞凋亡率，免疫组化法检测bcl-2、p53蛋白表达，应用RT-PCR法检测HL-60细胞中p53 mRNA表达。结果 不同浓度的As4S4作用12 ~ 48 h后，可显著抑制HL-60细胞的生长，呈时间浓度依赖性，并诱导细胞发生凋亡，凋亡率为30.18 % ~ 70.98 %，不同作用时间、不同浓度间凋亡率差异有统计学意义（P＜0.01），RT-PCR结果显示As4S4作用24 h后，下调p53 mRNA的表达。免疫组化结果显示，bcl-2、p53蛋白表达逐渐降低，并呈浓度依赖性。结论 As4S4能够显著抑制HL-60细胞的生长。诱导其凋亡，并下调bcl-2、p53的表达，可能是其重要机制。

Growth-inhibitory effects of As4S4 on leukemia cells and its mechanisms

Objective To study the growth-inhibitory effects of As4S4 on human leukemia cell line HL-60 cells in vitro and its molecular mechanisms. Methods The growth inhibition rates of HL-60 cells, after being treated with 7.5~60 mmol/L As4S4 12~48 h, were examined by MTT assary. The apoptosis rate was detected by flow cytometry(FCM), The protein expression levels of bcl-2, p53 in HL-60 cells were examined by SP Immunohistochemistry. The expression of p53 on HL-60 cell were checked by RT-PCR. Results As4S4 selectively inhibite proliferation of HL-60 cell line in a dose-and time-depended manner. Inhibitory rate was 36.05 % ~ 80.36 %(P <0.01). Of HL-60 cells, the apoptosis rates were 30.18 % ~ 70.98 % by flow cytometery (FCM). the down regulation of p53 expression was observed within 24 h after the treatment in As4S4 by RT-PCR. The expression of bcl-2 and p53 was decreased, with the increase of concentration and the ex－pression down regulation dose-and dependent. Conclusion As4S4 could could significantly inhibit the growth of HL-60 cells. The induction apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of its molecular mechanisms.