雄黄抑制卵巢癌细胞株SKOV3增殖和诱导凋亡的体外研究

Inhibition of cell proliferation and cell apoptosis on ovarian cancer cells SKOV3 by tetraarsenic tetrasulfide in vitro

目的研究中药雄黄主要成分As4S4对卵巢癌细胞株SKOV3细胞的增殖抑制和诱导凋亡的作用及其机制。方法 不同浓度As4S4（20pμmol／L、40Iμmol／L、60pμmol／L、80pμmol／L），处理SKOV3细胞24h，48h，72h后，透射电镜观察细胞形态变化；MTY法测定细胞增殖抑制率；流式细胞仪检测细胞凋亡率和细胞周期变化；RT—PCR法和Westernblot法检测As4S4对卵巢癌细胞株SKOV3细胞Bcl-2和Bax mRNA和蛋白的表达影响。结果 不同浓度As4S4处理的卵巢癌细胞株SKOV3，细胞增殖受到抑制，作用呈明显的浓度、时间依赖性，差异有统计学意义（P〈0．01）；流式细胞仪进行细胞周期DNA成分分析结果显示，随着As4S4浓度的增加SKOV3细胞G0／G1期细胞百分比明显降低，S期细胞百分比上升；Bcl一2的表达随药物作用浓度的增加而递减，Bax的表达随药物作用浓度的增加而增强。结论 四硫化四砷具有抑制SKOV3细胞生长增殖的作用，其作用机制与诱发细胞凋亡和调节Bcl一2与Bax表达有关。

Objective To study the inhibition effect and mechanism of As4S4 （Tetraarsenic Tetrasulfide） on ovarian cancer SKOV3 cells＇ proliferation and cell apoptosis. Methods SKOV3 cell lines were treated with different concentration of As4S4 ,MTF method was used to examine the inhibition of SKOV3 cells by AS4S4. Transmission electron microscope was used to observe morphologic change of apoptosis and flow cytometry（FCM） assay was performed to measure change of cell apoptosis rate and cell cycle. RT - PCR method and Westernblot was used to detect the mRNA and protein expression of Bcl -2 and Bax. Results SKOV3 cell proliferation was inhibited dependenting on time and concentration（ P 〈 0.01 ）. Flow cytometry （FCM）assay indicated that As4S4 could induce the apoptosis of SKOV3 cells, where cells in G0/G1 stage reduced, while cells in S stage increased. The expression of Bcl -2 was reduced,while the expression of Bax was increased. Conclusion As4 S4 is effective to inhibit the proliferation of SKOV3 cells, and the mechanism might he relevant to induction of cell apoptosis and regulatingthe expressions of Bcl -2 and Bax.