柚皮素通过PI3K/AKT/NF-κB通路抑制卵巢癌细胞增殖和侵袭、诱导凋亡作用的研究  

Study on effects of naringenin on inhibiting proliferationand invasion of ovarian cancer cells and inducing apoptosis by PI3K/AKT/NF-κB pathway

作　　者：齐冰丽 黄平[1] 颜瑞雪 李倩[1] QI Bingli;HUANG Ping;YAN Ruixue;LI Qian(First Department of Gynecology, Cangzhou Central Hospital, Cangzhou 061000, Hebei, China)

机构地区：[1]沧州市中心医院妇一科

出　　处：《中国临床药理学与治疗学》2019年第11期1234-1241,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：沧州市重点研发计划指导项目(172302019)

摘　　要：目的:探究柚皮素(NAR)通过PI3K/AKT/NF-κB通路抑制卵巢癌细胞增殖、凋亡和侵袭能力的机制。方法:体外培养卵巢癌细胞,并分为空白组、低剂量柚皮素组、中剂量柚皮素组和高剂量柚皮素组;使用柚皮素预处理后,检测NAR对卵巢癌细胞增殖、凋亡、侵袭及迁移的影响情况;检测细胞侵袭迁移及凋亡相关蛋白和PI3K/AKT/NF-κB通路相关蛋白的表达情况。结果:使用柚皮素处理后,各组卵巢癌细胞增殖、迁移、侵袭受到显著抑制,凋亡受到显著促进,且对柚皮素呈剂量依赖性。相比空白组,使用柚皮素各组PCNA、Bcl-2、N-cadherin、MMP-9、MMP-2蛋白水平显著降低(P<0.01),Bax、Caspase-3、E-cadherin、PI3K蛋白表达水平及AKT、p65磷酸化水平显著升高(P<0.01),且随着柚皮素使用剂量的增加呈剂量依赖性,总AKT蛋白表达无显著变化(P>0.05)。结论:NAR可能通过抑制EMT及PI3K/AKT/NF-κB通路抑制卵巢癌细胞增殖和侵袭能力,并促进卵巢癌细胞的凋亡,在一定剂量范围内呈剂量依赖性。AIM:To investigate the mechanism of naringenin(NAR)inhibiting the proliferation,apoptosis and invasion ability of ovarian cancer cells by PI3K/AKT/NF-κB pathway.METHODS:Ovarian cancer cells were cultured in vitro.They were divided into blank group(Control),low-dose NAR group,medium-dose NAR group and high-dose NAR group.After pretreatment with NAR,effects of NAR on proliferation,apoptosis,invasion and migration of ovarian cancer cells were detected.The expression of invasion,migration and apoptosis related proteins and PI3K/AKT/NF-κB pathway-related proteins was detected.RESULTS:The proliferation,migration and invasion of ovarian cancer cells were significantly inhibited in groups treated with NAR,while apoptosis was significantly promoted,showing dose-dependence to NAR.Compared with blank group,levels of PCNA,Bcl-2,N-cadherin,MMP-9 and MMP-2 protein were significantly decreased in the groups treated with NAR(P<0.01),while expression levels of Bax,Caspase-3,E-cadherin and PI3K protein,phosphorylation level of AKT and p65 were significantly increased(P<0.01).With increase of NAR dose,there was dose-dependence.There was no significant change in total AKT protein expression(P>0.05).CONCLUSION:NAR may inhibit proliferation and invasion ability of ovarian cancer cells by inhibiting EMT and PI3K/AKT/NF-κB pathway,and promote apoptosis of ovarian cancer cells,showing dose-dependence within a certain dose range.

关 键 词：卵巢癌 柚皮素 PI3K/AKT/NF-κB通路 细胞凋亡 

分 类 号：R965.2[医药卫生—药理学] R737.3[医药卫生—药学]