药用植物珍珠菜提取物ZE4调控卵巢癌细胞增殖、侵袭和迁移的分子机制  

Molecular Mechanisms of Lysimachia clethroides Extract ZE4 Regulating Proliferation,Invasion and Migration of Ovarian Cancer Cells

作　　者：郑玲 刘杏 刘雨 易黎明 陈义萍 鞠晓军 Zheng Ling;Liu Xing;Liu Yu;Yi Liming;Chen Yiping;Ju Xiaojun(Clinical Skills Training Center,Hunan University of Medicine,Huaihua,418000;Department of Human Anatomy,Hunan University of Medicine,Huaihua,418000)

机构地区：[1]湖南医药学院临床技能实训中心,怀化418000 [2]湖南医药学院人体解剖学教研室,怀化418000

出　　处：《分子植物育种》2022年第6期2043-2049,共7页Molecular Plant Breeding

基　　金：国家中医药《药用植物生化性状育种目标以及生物活性物质医学功能研究》专项(2020ZYY03-12)资助。

摘　　要：珍珠菜是中国传统中药,含有异槲皮苷、黄芪甲素、槲皮素、山奈酚、芦丁等黄酮类成分,珍珠菜具有抗肿瘤、抗氧化、保肝、抗菌等活性。本研究试图探讨珍珠菜提取物ZE4对卵巢癌细胞增殖、侵袭和迁移的影响及其相关机制。研究表明,与对照组相比,不同浓度的ZE4处理的A2780细胞增殖抑制率显著提高(P<0.05),且呈现出剂量、时间依赖性。不同浓度ZE4较对照组明显降低A2780细胞侵袭数和迁移数、CyclinD1、MMP-2、p-Akt蛋白水平(P<0.05),显著提高E-cadherin、p-FoxO3a蛋白表达量(P<0.05),均呈剂量依赖性。抑制剂LY294002作用于A2780细胞后,相比于对照组,细胞增殖抑制率、E-cadherin、p-FoxO3a蛋白水平显著升高(P<0.05),细胞侵袭数、迁移数和CyclinD1、MMP-2、p-Akt蛋白水平明显下降(P<0.05)。与ZE4 (75μg/mL)组比较,IGF-1和ZE4组细胞增殖抑制率、E-cadherin和p-FoxO3a蛋白水平降低,细胞侵袭数、迁移数和CyclinD1、MMP-2、p-Akt蛋白表达量增加,差异均达到显著水平(P<0.05)。本研究初步表明,珍珠菜提取物ZE4通过磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)/叉头转录因子O3a (FoxO3a)信号通路抑制卵巢癌细胞增殖、侵袭和迁移。Lysimachia clethroides is a traditional Chinese medicine.It contains isoquercetin,Astragalus a,quercetin,kaempferol,rutin and other flavonoids.Lysimachia has anti-tumor,antioxidant,liver protection,antibacterial and other activities.This study attempts to investigate the effects of Lysimachia clethroides extract ZE4 on proliferation,invasion and migration of ovarian cancer cells and its related mechanism.Compared with the control group,the proliferation inhibition rate of A2780 cells treated with ZE4 at different concentrations was significantly enhanced(P<0.05),showing a dose-dependent and time-dependent manner.ZE4 at different concentrations dramatically decreased the number of invasion and migration of A2780 cells,the levels of CyclinD1,MMP-2 and p-Akt protein(P<0.05),and remarkably increased the expression of E-cadherin and p-FoxO3(P<0.05),all in a dose-dependent manner.After the inhibitor LY294002 acted on A2780 cells,compared with the control group,the cell proliferation inhibition rate,E-cadherin and p-FoxO3a protein levels were obviously raised(P<0.05),and the number of cell invasion,migration,CyclinD1,MMP-2 and p-Akt protein levels were notably decreased(P<0.05).Compared with ZE4 group(75 μg/mL),the cell proliferation inhibition rate,E-cadherin and p-FoxO3a protein levels in IGF-1 and ZE4 groups were reduced,and the number of cell invasion,migration,CyclinD1,MMP-2 and p-Akt protein expressions were improved,and all differences reached significant levels( P <0.05).Lysimachia clethroides extract ZE4 inhibits the proliferation,invasion and migration of ovarian cancer cells through the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/forkhead box O3a(FoxO3a) signaling pathway.

关 键 词：珍珠菜 珍珠菜提取物ZE4 卵巢癌 增殖 侵袭 迁移 

分 类 号：R285[医药卫生—中药学]