葫芦素E对卵巢癌细胞增殖的抑制作用及其机理研究  

Inhibitory effect of cucurbitacin E on the proliferation of ovarian cancer cells and its mechanism

作　　者：单晓蕾[1] 周雪莹[1] 杨姣[1,2] 王艳丽[1] 邓意辉[3] 张美侠[1] 

机构地区：[1]中国医科大学药学院临床药理教研室,辽宁沈阳110001 [2]黑龙江大庆油田总医院药学部,黑龙江大庆163001 [3]沈阳药科大学药剂教研室,辽宁沈阳110015

出　　处：《癌症》2010年第1期20-24,共5页Chinese Journal of Cancer

基　　金：辽宁省自然科学基金(No.20082092)~~

摘　　要：背景与目的:葫芦素E(cucurbitacin E,CuE)具有抗肿瘤、抗化学致癌、保肝、提高机体免疫力等多种生物活性。本研究以人卵巢癌细胞系ES-2为靶细胞,观察CuE对ES-2细胞的增殖抑制和凋亡诱导作用,探讨其作用机理。方法:MTT法检测不同浓度CuE处理ES-2细胞24、48h和72h后的细胞增殖情况,倒置显微镜和荧光显微镜观察细胞形态学变化和细胞凋亡,流式细胞仪检测细胞周期分布,Western blot检测CuE对细胞内磷酸化STAT3表达的影响。结果:CuE抑制ES-2细胞增殖,增加CuE浓度和延长作用时间可使抑制作用增强。流式细胞仪检测显示,1μmol/LCuE作用ES-2细胞24h后,处于S期和G2/M期的细胞比例明显升高,分别由(10.55±0.91)%、(16.31±4.61)%上升至(18.53±1.43)%、(58.34±5.77)%,同时伴随G1期细胞由(73.13±4.70)%降至(23.12±5.45)%,差异有统计学意义(P<0.05)。荧光显微镜显示CuE处理组出现典型的细胞凋亡。Westernblot结果显示CuE可降低磷酸化STAT3的表达,并随CuE浓度升高作用增强。结论:CuE可抑制ES-2细胞的增殖、诱导细胞凋亡和引起细胞周期阻滞,该作用可能与细胞内磷酸化STAT3表达下降有关。Background and Objective：There are various biological activities of cucurbitacin E （CuE）,including antitumor effect,anti-chemical carcinogenesis,liver-protection,and enhancement of the immunity,and so on.This study was to investigate the effect of CuE on proliferation inhibition and apoptosis induction of ovarian cancer ES-2 cells,and to explore the mechanism.Methods：ES-2 cells were treated with different concentrations of CuE for 24,48,and 72 h,respectively,and cell proliferation was detected by MTT assay.The morphological changes and apoptosis were observed under inverted microscopy and fluorescent microscopy.Cell cycle distribution was analyzed by flow cytometry.The expression of pSTAT3 was determined by Western blot.Results：The number of ES-2 cells significantly decreased as the concentration of CuE increased or the time prolonged.Flow cytometry analysis showed that the ratio of ES-2 cells treated with 1 μmol /L CuE for 24 h increased both in S phase [from （10.55±0.91）% to （16.31±4.61）%] and in G2/M phase [from （18.53±1.43）% to （58.34±5.77）%],while decreased in G1 phase [from （73.13±4.70）% to （23.12±5.45）% ] （P〈0.05）.The marked morphological changes of cell apoptosis were clearly observed in ES-2 cells treated with CuE.CuE inhibited the STAT3 phosphorylation in ES-2 cells in a dose-dependent manner.Conclusion：CuE can inhibit ES-2 cell proliferation and induce apoptosis and cell cycle arrest,which may be related to the decreased expression of the intracellular STAT3 phosphorylation.

关 键 词：葫芦素E 卵巢肿瘤 ES-2细胞 细胞凋亡 

分 类 号：R737.31[医药卫生—肿瘤]