科罗索酸抑制人卵巢癌细胞SKOV-3过度增殖和诱导细胞凋亡  

Corosolic Acid Inhibits Excess Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells SKOV-3

作　　者：孙喆 王钧峰 李会影 姚慧欣 SUN Zhe;WANG Junfeng;LI Huiying;YAO Huixin(Department of Obstetrics and Gynecology,Red Flag Hospital Affiliated to Mudanjiang Medical College,Mudanjiang,Heilongjiang,157011,China;Department of Orthopedics,Red Flag Hospital Affiliated to Mudanjiang Medical College,Mudanjiang,Heilongjiang,157011,China;Medical Department,Red Flag Hospital Affiliated to Mudanjiang Medical College,Mudanjiang,Heilongjiang,157011,China)

机构地区：[1]牡丹江医学院附属红旗医院妇产科,黑龙江省牡丹江市157011 [2]牡丹江医学院附属红旗医院骨科,黑龙江省牡丹江市157011 [3]牡丹江医学院附属红旗医院医务科,黑龙江省牡丹江市157011

出　　处：《医学分子生物学杂志》2024年第1期45-50,共6页Journal of Medical Molecular Biology

基　　金：黑龙江省卫生健康委科研课题(No.2018335)。

摘　　要：目的探究科罗索酸(corosolic acid,CRA)对人卵巢癌细胞SKOV-3增殖和凋亡的作用及机制。方法将细胞分为空白对照(Ctrl)组、CRA(10μmol/L)、CRA(20μmol/L)、CRA(50μmol/L)组,使用相应浓度的CRA处理细胞,CCK-8检测细胞增殖,流式细胞术检测细胞凋亡,蛋白质印迹检测抗原Ki67(Ki67)、周期蛋白D1(cyclin D1)、周期蛋白依赖性激酶6(cyclin-dependent kinases 6,CDK6)、B细胞淋巴瘤(Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、活化型半胱天冬酶3(cleaved caspase-3)、cleaved caspase-9、磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)、蛋白激酶B(protein kinase B,AKT)、p-AKT蛋白表达,构建SKOV-3裸鼠移植瘤模型并记录肿瘤体积,免疫组化检测Ki67和血管内皮生长因子(vascular endothelial growth factor,VEGF)阳性细胞率。结果在细胞实验中,与Ctrl组比较,CRA(10μmol/L)、CRA(20μmol/L)、CRA(50μmol/L)组细胞增殖水平显著降低,Bcl-2/Bax、p-AKT/AKT比率降低,Ki67、Cyclin D1、CDK6、PI3K蛋白表达水平降低,同时细胞凋亡水平显著升高,cl-caspase-3和cl-caspase-9蛋白表达水平升高。在动物实验中,与Ctrl组比较,CRA(10μmol/L)、CRA(20μmol/L)、CRA(50μmol/L)组肿瘤体积显著降低,Ki67和VEGF阳性细胞率显著降低。结论科罗索酸可抑制人卵巢癌细胞SKOV-3的过度增殖,并诱导细胞凋亡,起作用机制可能与抑制PI3K/AKT信号通路有关。Objective To investigate the effect of corosolic acid(CRA)on the proliferation and apoptosis of human ovarian cancer cells SKOV-3 and its mechanism.Methods Cells were divided into 4 groups:Ctrl group,CRA-10μmol/L group,CRA-20μmol/L group,and CRA-50μmol/L groups,each group was treated with corresponding concentration of CRA.CCK-8 assay was used to measure cell growth.Flow cytometry was used to detect cell apoptosis.The protein expression levels of Ki67,Cyclin D1,CDK6,Bcl-2,Bax,cleaved-caspase-3,cleaved-caspase-9,PI3K,AKT,p-AKT were determined by Western blotting.In addition,the cell line derived xenograft model was established by transplanting the human ovarian cancer cells SKOV-3 in nude mice,the volume of the tumors from the nude mice were measured,the rates of Ki67 or VEGF positive cells were detected by immunohistochemistry.Results In cytological experiments,the cell growth levels,the Bcl-2/Bax and p-AKT/AKT ratios,the protein expression levels of Ki67,Cyclin D1,CDK6,PI3K in the CRA groups(10,20,50μmol/L)were decreased significantly,and the cell apoptosis rate,protein expression levels of cleaved-caspase-3 and cleaved-caspase-9 were increased notably,when compared with those in the Ctrl group.In animal experiments,the tumor volume,the rates of Ki67 or VEGF positive cells in the CRA groups(10,20,50μmol/L)were decreased markedly,when compared with those in the Ctrl group.Conclusion Corosolic acid can inhibit the excess proliferation of SKOV3 cells,and induce their apoptosis,the mechanism may related to the inhibition of PI3K/AKT signaling pathway.

关 键 词：科罗索酸 卵巢癌 细胞增殖 细胞凋亡 PI3K/AKT 

分 类 号：R737.31[医药卫生—肿瘤]