吴茱萸碱抑制人卵巢癌细胞SKOV3增殖的实验研究  

Evodiamine inhibits the proliferation of ovarian cancer SKOV3 cells in vitro and in vivo

作　　者：刘惠玉 李方[2] 

机构地区：[1]茌平县人民医院,茌平252100 [2]山东大学附属济南市中心医院,济南250014

出　　处：《现代妇产科进展》2015年第6期428-430,434,共4页Progress in Obstetrics and Gynecology

摘　　要：目的:探讨吴茱萸碱对人卵巢癌细胞SKOV3增殖的抑制作用及其机制。方法:采用噻唑蓝(MTT)法检测不同浓度吴茱萸碱对SKOV3细胞增殖活性的影响;采用Annexin V-FITC/PI染色检测吴茱萸碱对SKOV3细胞凋亡的影响;Western blot法检测吴茱萸碱对SKOV3细胞内caspase-3和PARP活化的影响。构建卵巢癌SKOV3裸鼠移植瘤模型并给予吴茱萸碱灌胃,绘制肿瘤生长曲线、称取瘤重,检测肿瘤组织中caspase-3和PARP活化情况。结果:0.5、1、2、4μmol/L吴茱萸碱处理SKOV3细胞24h后,细胞活性较对照组分别减少(15.95±1.61)%、(33.82±4.03)%、(46.62±5.45%)和(63.82±5.42)%,且呈明显时间和浓度依赖性;0.5、1、2μmol/L吴茱萸碱作用SKOV3细胞24h诱导细胞凋亡率分别为(12.93±3.81)%、(26.27±3.31)%和(36.72±4.73)%,均高于对照组(8.08±1.04,P<0.05);吴茱萸碱显著活化SKOV3细胞内caspase-3和PARP,诱导细胞凋亡发生。成功构建卵巢癌裸鼠皮下移植瘤模型,给药14天后裸鼠皮下移植瘤体积明显小于对照组(P<0.01),给药21天后移植瘤体积较对照组减少54.01%(P<0.01)、瘤重减少42.03%(P<0.01),给药组裸鼠移植瘤蛋白内cleaved caspase-3和cleaved PARP小片段活化部分显著增多。结论:吴茱萸碱显著抑制人卵巢癌细胞SKOV3体外增殖和裸鼠皮下移植瘤生长,其作用机制与吴茱萸碱诱导细胞凋亡密切相关。Objective：To explore the effects of evodiamine on the proliferation of ovari-an cancer SKOV3 cells and the underlying mechanisms. Methods：MTT assay was used to in-vestigate the cytotoxic effects of evodiamine on SKOV3 cells. Annexin V-FITC/PI staining and Western blot were used to investigate the evodiamine-induced apoptosis in SKOV3 cells. A tumor xenograft model was used to investigate the inhibitory effects of evodiamine on SKOV3 cells in vivo. Results：Evodiamine significantly inhibited the proliferation of SKOV3 cells in vitro,in a time-and dose-dependent manner. Evodiamine significantly induced apoptosis in SK-OV3 cells,accompanied by an increase of Annexin V-positive cells,as well as a evidently cleav-age of caspase-3 and PARP. Daily treatment of evodiamine led to a substantial inhibition of tumor growth in ovarian cancer xenograft model with concomitant cleavage of caspase-3 and PARP. Conclusion：The in vitro and in vivo results demonstrate that evodiamine efficiently sup-presses the proliferation of ovarian cancer SKOV3 cells and suggest that evodiamine may be a potential therapeutic agent for the treatment of ovarian cancer.

关 键 词：吴茱萸碱 卵巢癌 凋亡 增殖 

分 类 号：R737.33[医药卫生—肿瘤]