TRB3调控TGF-β1/Smad3/PAI-1轴对胃癌细胞功能的影响  

Effect of TRB3 on the Function of Gastric Cancer Cells by Regulating TGF-β1/Smad3/PAI-1 Axis

作　　者：叶宇 尹雪峰 YE Yu;YIN Xuefeng(Department of General Surgery,Zhejiang Integrated Traditional Chinese and Western Medicine Hospital,Zhejiang 310003,China)

机构地区：[1]浙江省中西医结合医院(杭州市红十字会医院)普外科,310003

出　　处：《医学研究杂志》2023年第12期93-98,共6页Journal of Medical Research

基　　金：浙江省医药卫生科技计划项目(2019KY135)。

摘　　要：目的研究TRB3通过调控TGF-β1/Smad3/PAI-1轴对胃癌细胞功能的影响。方法采用Western blot法检测TRB3蛋白在胃癌细胞系(AGS、HGC-27、NCI-N87、SNU5和MKN45)和正常人胃黏膜细胞GES-1中的表达。敲低胃癌细胞AGS TRB3,采用CCK-8、荧光激活细胞分选仪(fluorescenceactivated cell sorter,FACS)、Transwell实验、划痕实验和Western blot法分别检测胃癌细胞增殖、凋亡、侵袭、迁移情况和TGF-β1/Smad3/PAI-1信号通路蛋白的改变;在此基础上进行转化生长因子-β1(transforming growth factor-β1,TGF-β1)处理,再次重复上述实验。结果与GES-1细胞比较,胃癌细胞系中TRB3蛋白表达增多。下调胃癌细胞TRB3,细胞增殖能力下降,活力降低(52%±12%,P<0.001);迁移能力下降,细胞愈合率降低(24%±6%,P<0.001);侵袭能力下降,侵袭细胞数降低(107±23,P<0.001);TGF-β1/Smad3/PAI-1通路被抑制,TGF-β1、p-SMAD3和PAI-1表达减少;细胞凋亡增多,凋亡细胞比例升高(17%±3%,P<0.001);在此基础上进行TGF-β1处理,细胞增殖能力增强,细胞活力升高(73%±10%,P<0.01);迁移能力增强,细胞愈合率升高(63%±8%,P<0.01);侵袭能力增强,侵袭细胞数升高(252±20,P<0.01);细胞凋亡减少,凋亡比例降低(12%±2%,P<0.01)。结论TRB3通过激活TGF-β1/Smad3/PAI-1信号通路促进胃癌发展。Objective To study the effect of TRB3 on gastric cancer cells function by regulating TGF-β1/Smad3/PAI-1 axis.Methods The expression of TRB3 protein in gastric cancer cell lines(AGS,HGC-27,NCI-N87,SNU5 and MKN45)and normal human gastric mucosal cells(GES-1)was detected by Western blot.Knockdown of TRB3 in gastric cancer cell AGS,CCK-8,fluorescenceactivated cell sorter(FACS),Transwell assay,scratch assay and Western blot were used to detect cell proliferation,apoptosis,invasion,migration and the changes of TGF-β1/Smad3/PAI-1signal pathway proteins.On the basis of knockdown of TRB3,TGF-β1 treated gastric cancer cell AGS,and the above experiments were repeated again.Results Compared with GES-1 cells,the expression of TRB3 protein increased in gastric cancer cell lines.the proliferation ability and the viability of cells(52%±12%,P<0.001)were decreased;migration ability and cell healing rate(24%±6%,P<0.001)were decreased;the invasive ability and the number of invasive cells(107±23,P<0.001)were decreased;TGF-β1/Smad3/PAI-1 pathway was inhibited,and the expression of TGF-β1,p-SMAD3 and PAI-1 were decreased;the apoptosis and the proportion of apoptotic cells(17%±3%,P<0.001)were increased.On the basis of knockdown of TRB3,TGF-β1 was used to treated gastric cancer cells AGS,the cell viability(73%±10%,P<0.01)was increased;the migration ability and cell healing rate(63%±8%,P<0.01)were increased;the number of invasive cells(252±20,P<0.01)was increased;cell apoptosis and the percentage of apoptosis(12%±2%,P<0.01)was reduced.Conclusion TRB3 promotes the development of gastric cancer by activating of TGF-β1/Smad3/PAI-1signaling pathway.

关 键 词：胃癌 TRB3 增殖 TGF-β1/Smad3/PAI-1轴 

分 类 号：R735.2[医药卫生—肿瘤]