紫草素化学预防子宫内膜癌的作用机制  

Mechanism of Chemoprevention of Endometrial Cancer by Shikonin

作　　者：黄彩梅 陈建凤 余思云 李铭旸 胡国华[4] HUANG Caimei;CHEN Jianfeng;YU Siyun;LI Mingyang;HU Guohua(Maternity&Infant Health Hospital Affiliated to East China Normal University/Traditional Chinese Medicine Department,Shanghai Changning Maternity&Infant Health Hospital,Shanghai 200051,China;Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200083,China;TCM Gynecology,Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]华东师范大学附属妇幼保健院/上海市长宁区妇幼保健院中医科,上海200051 [2]上海中医药大学附属龙华医院,上海200032 [3]上海中医药大学附属岳阳中西医结合医院,上海200083 [4]上海中医药大学附属市中医医院中医妇科,上海200071

出　　处：《世界中医药》2023年第5期606-612,619,共8页World Chinese Medicine

基　　金：国家自然科学基金青年基金项目(82004159);上海市2020年度“科技创新行动计划”医学创新研究专项项目(20Z21900400)。

摘　　要：目的:基于核因子E_(2)相关因子2(Nrf2/NQO1)信号通路探讨紫草素(SK)对子宫内膜癌的化学预防作用机制。方法:体外实验,采用四甲基偶氮唑盐比色(MTT)法检测SK对人子宫内膜癌细胞(Ishikawa)的抑制作用;用蛋白质印迹法(Western Blotting)检测SK对Ishikawa细胞NQO1、Nrf2、γ-谷氨酰半胱氨酸合成酶(γGCS)蛋白表达水平。体内实验,构建子宫内膜癌Ishikawa细胞裸鼠移植瘤动物模型,分为SK组、甲地孕酮组、对照组。计算各组的肿瘤抑制率;实时聚合酶链式反应(RT-PCR)法检测肿瘤组织中NQO1、Nrf2、磷脂酰肌醇3-激酶(PI3K)mRNA表达水平。结果:体外实验表明SK对Ishikawa细胞增殖有抑制作用,且具有时间和浓度依赖性(P<0.05)。雌激素环境下SK具有促进Nrf2/ARE信号通路相关蛋白表达的作用。体内结果表明SK组对Ishikawa细胞移植瘤生长有抑制作用。RT-PCR法结果显示表明SK在体内能激活PI3K/AKT信号通路。结论:SK参与子宫内膜癌Ishikawa细胞Nrf2/NQO1信号通路的激活,可能通过防止雌激素氧化还原反应发挥化学预防子宫内膜癌发生的作用。Objective:To investigate the chemopreventive mechanism of shikonin(SK)on endometrial cancer based on the nuclear factor E 2-related factor 2(Nrf2)/quinone oxidoreductase-1(NQO1)signaling pathway.Methods:In vitro experiments were conducted to detect the inhibitory effect of SK on human endometrial cancer cells(Ishikawa)with the methylthiazolyl tetrazolium(MTT)method.The Western blotting assay was used to detect the effects of SK on NQO1,Nrf2,andγ-glutamyl cysteine synthetase(γGCS)protein expression levels.In vivo experiments were conducted to construct an animal model of endometrial cancer Ishikawa cell transplanted tumor in nude mice.The model mice were divided into a SK group,a megestrol group,and a control group.The tumor inhibition rate of each group was calculated,and the Real-time polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels of NQO1,Nrf2,and phosphatidylinositol 3-kinase(PI3K)in tumor tissues.Results:In vitro experiments showed that SK inhibited the proliferation of Ishikawa cells in a time-and concentration-dependent manner(P<0.05)and promoted the expression of proteins related to the Nrf2/ARE signaling pathway under the estrogenic environment.In vivo results indicated that the SK group could inhibit the growth of transplanted tumors in Ishikawa cells.The results of RT-PCR showed that SK could activate the PI3K/AKT signaling pathway in vivo.Conclusion:SK is involved in the activation of the Nrf2/NQO1 signaling pathway in endometrial cancer Ishikawa cells,which plays a chemopreventive role in the occurrence of endometrial cancer by preventing estrogen redox reactions.

关 键 词：子宫内膜癌 紫草素 氧化应激 Nrf2/NQO1信号通路 ISHIKAWA细胞 裸鼠移植瘤 化学预防 雌激素依赖性肿瘤 

分 类 号：R285.5[医药卫生—中药学]