TRIM45靶向IGF-1R抑制乳癌MCF-7细胞增殖和迁移的机制  

Mechanism of TRIM45 targeting IGF-1R to inhibit proliferation and migration of breast cancer MCF-7 cells

作　　者：曹璨 董晓雷 李双 李冰[1] CAO Can;DONG Xiaolei;LI Shuang;LI Bing(Department of Genetics and Cell Biology,School of Basic Medicine,Qingdao University,Qing-dao 266071,China)

机构地区：[1]青岛大学基础医学院遗传学与细胞生物学系,山东青岛266071

出　　处：《青岛大学学报（医学版）》2024年第2期164-168,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81871231)。

摘　　要：目的探究三结构域蛋白45(TRIM45)通过靶向胰岛素样生长因子1受体(IGF-1R)抑制人乳癌MCF-7细胞增殖和迁移的作用机制。方法将人乳癌MCF-7细胞分为TRIM45过表达组、空载对照组及阴性对照组。通过细胞增殖实验及划痕实验进行细胞增殖及迁移能力检测,采用蛋白质免疫印迹(WB)法检测自噬相关蛋白p62、微管相关蛋白Ⅰ轻链3B(LC3B)、自噬相关蛋白8(ATG8)的表达,通过免疫沉淀实验分析TRIM45与IGF-1R的结合,采用WB法检测促增殖蛋白IGF-1R和簇集蛋白(CLU)的表达。结果与空载对照组相比较,TRIM45过表达组不同时间的细胞增殖率及迁移率均显著降低(F=19.87~177.91,P<0.05)。与空载对照组相比较,TRIM45过表达组细胞自噬相关蛋白p62的表达显著降低,LC3B和ATG8的表达显著增加(F=22.97~113.50,P<0.05)。TRIM45可以与IGF-1R结合,并且TRIM45过表达组细胞IGF-1R及CLU蛋白表达较空载对照组显著降低(F=51.06、30.45,P<0.05)。结论TRIM45可以与IGF-1R结合,抑制IGF-1R及CLU的表达,诱导乳癌细胞自噬,抑制乳癌细胞的增殖和迁移能力。Objective To investigate the mechanism of tripartite motif-containing protein 45(TRIM45)inhibiting the proliferation and migration of human breast cancer MCF-7 cells by targeting insulin-like growth factor-1 receptor(IGF-1R).[WTHX]Methods Human breast cancer MCF-7 cells were divided into TRIM45 overexpression group,empty vector control group,and negative control group.Cell proliferation and migration abilities were determined using the cell proliferation test and scratch test.Western blot(WB)was used to measure the expression of autophagy-related protein p62,microtubule-associated protein 1 light chain 3B(LC3B),and autophagy-related protein 8(ATG8).The binding of TRIM45 with IGF-1R was analyzed by immunoprecipitation assay.The expression of IGF-1R and clusterin(CLU)was measured by WB.Results Compared with those in the empty vector control group,the proliferation rate and migration rate of MCF-7 cells in the TRIM45 overexpression group were significantly decreased(F=19.87-177.91,P<0.05).Compared with the empty vector control group,the TRIM45 overexpression group showed significantly decreased expression of p62 and significantly increased expression of LC3B and ATG8(F=22.97-113.50,P<0.05).TRIM45 could bind to IGF-1R.The protein expression of IGF-1R and CLU was significantly lower in the TRIM45 overexpression group than in the empty vector control group(F=51.06,30.45,P<0.05).Conclusion TRIM45 can bind to IGF-1R to inhibit the expression of IGF-1R and CLU,inducing the autophagy of breast cancer cells to inhibit the proliferation and migration of breast cancer cells.

关 键 词：乳腺肿瘤 三结构域蛋白45 受体 IGF 1型 细胞增殖 细胞运动 

分 类 号：R737.9[医药卫生—肿瘤] R329.25[医药卫生—临床医学]