姜黄素通过调控TGF-β1/Smad信号通路抑制恶性胶质瘤生长的作用机制  

Functional mechanism of curcumin inhibiting growth of malignant glioma by regulating TGF-β1/Smad signaling pathway

作　　者：赵岗[1] 张国栋[1] 王理想 李远超 周虎[2] 程振国[1] ZHAO Gang;ZHANG Guo-dong;WANG Li-xiang;LI Yuan-chao;ZHOU Hu;CHENG Zhen-guo(Dept of Neurosurgery,Xinxiang Central Hospital,Xinxiang,Henan 453000,China;Department of Hematology,Henan Cancer Hospital,Zhengzhou 450003,China)

机构地区：[1]新乡市中心医院神经外科,河南新乡453000 [2]河南省肿瘤医院血液科,河南郑州450003

出　　处：《中国药理学通报》2024年第11期2113-2118,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82070120);河南省医学科技攻关计划联合共建项目(No LHGJ20210910)。

摘　　要：目的探究姜黄素对恶性胶质瘤生长的影响及可能机制。方法以人恶性胶质瘤细胞U87为研究对象,随机分为空白对照组(无任何干预)、姜黄素低、中、高(10、20、40μmol·L^(-1))、替莫唑胺组(40μmol·L^(-1))、姜黄素40μmol·L^(-1)+LY210976110μmol·L^(-1)、姜黄素40μmol·L^(-1)+SRI-01138110μmol·L^(-1),干预48 h。CCK-8法、Transwell法对各组U87细胞活性、迁移及侵袭能力测定,经由流式细胞术测定U87细胞周期变化,Western blot法测定U87细胞TGF-β1/Smad信号通路相关蛋白表达水平。结果姜黄素组与替莫唑胺组干预48 h后U87细胞活性百分比、细胞迁移及侵袭数目均低于空白对照组(P<0.05),且均随姜黄素剂量增大而下降(P<0.05)。对比空白对照组,姜黄素组及替莫唑胺组Sub-G_(0)期细胞数增多(P<0.05),G_(2)/M期细胞数减少(P<0.05)。姜黄素高剂量组及替莫唑胺组U87细胞TGF-β1、p-Smad 3、N-钙黏蛋白(N-cadherin)、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9蛋白相对表达量均低于空白对照组(P<0.05),Smad 7、E-钙黏蛋白(E-cadherin)蛋白相对表达量均高于空白对照组(P<0.05)。姜黄素高剂量组与替莫唑胺组各指标对比差异均无统计学意义(P>0.05)。相比姜黄素高剂量组,TGF-β1/Smad通路抑制剂能进一步抑制U87细胞活性、迁移及侵袭,降低TGF-β1、p-Smad 3、MMP-2、MMP-9蛋白相对表达量(P<0.05),提高Smad 7、E-cadherin蛋白相对表达量(P<0.05),而TGF-β1/Smad通路激活剂反之(P<0.05)。结论姜黄素能抑制恶性胶质瘤U87细胞生长,其机制可能与调控TGF-β1/Smad信号通路相关。Aim To explore the effect of curcumin on the growth of malignant glioma and the possible mechanism.Methods Human glioblastoma cell U87 was taken as the study object.They were randomly separated into the blank control group(without any intervention)and low,medium and high curcumin group(10,20 and 40μmol·L^(-1)),temozolomide group(40μmol·L^(-1)),curcumin 40μmol·L^(-1)+LY210976110μmol·L^(-1),curcumin 40μmol·L^(-1)+SRI-01138110μmol·L^(-1),then they were intervened for 48 h.The activity,migration and invasion ability of U87 cells in each group were measured by CCK-8 method and Transwell method.The cell cycle changes of U87 cells were measured by flow cytometry.The expression levels of TGF-β1/Smad signaling pathway in U87 cells were measured by Western blotting.Results After 48 h intervention,the percentage of U87 cell activity,cell migration and invasion number in curcumin group and temozolomide group were lower than those in the blank control group(P<0.05),and all decreased with the increase of curcumin dose(P<0.05).Compared with the blank control group,the number of cells increased in Sub-G_(0) stage in the curcumin group and temozolomide group(P<0.05),and decreased in G_(2)/M stage(P<0.05).The protein relative expression levels of TGF-β1,p-Smad 3,N-cadherin,matrix metalloproteinase(MMP)-2 and MMP-9 in U87 cells in high curcumin group and temozolomide group were lower than those in the blank control group(P<0.05),and the protein relative expression levels of Smad 7 and E-cadherin were higher than those in the blank control group(P<0.05).There was no statistically significant difference between the high curcumin group and temozolomide group(P>0.05).Compared with the high curcumin group,inhibition of TGF-β1/Smad pathway could further inhibit the activity,migration and invasion of U87 cells,reduce the relative expression levels of TGF-β1,P-Smad 3,MMP-2 and MMP-9 proteins(P<0.05),and increase the relative expression levels of Smad 7 and E-cadherin protein(P<0.05),while the TGF-β1/Smad pathway activator

关 键 词：恶性胶质瘤 姜黄素 U87 TGF-Β1/SMAD信号通路 细胞活性 

分 类 号：R285[医药卫生—中药学]