转化生长因子-β通路对胃癌细胞在裸鼠体内增殖、侵袭及slug蛋白和上皮钙黏素基因表达的影响  

Effect of transforming growth factor-βpathway on proliferation,invasion and expressions of slug protein and epithelial cadherin genes in gastric cancer cells of nude mice

作　　者：张子杭 成元华 ZHANG Zihang;CHENG Yuanhua(Department of Pathology,Binhai County People's Hospital,Yancheng,Jiangsu 224500,China;Department of Pathology,The Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou 550004,China)

机构地区：[1]滨海县人民医院病理科,江苏盐城224500 [2]贵州医科大学附属医院病理科,贵州贵阳550004

出　　处：《安徽医药》2023年第9期1804-1808,共5页Anhui Medical and Pharmaceutical Journal

基　　金：贵州省科技计划项目(黔合科J字[2009]2187号)。

摘　　要：目的研究转化生长因子-β(TGF-β)通路的激活与阻断对人胃癌HGC-27细胞增殖、侵袭及slug蛋白和上皮钙黏素(E-cad)基因表达的影响。方法于2021年4月至2022年3月使用人胃癌HGC-27细胞构建30只胃癌细胞裸鼠皮下移植瘤模型后,使用外源性通路激活剂TGF-β1和阻断剂SB431542对TGF-β通路进行激活和阻断。使用随机数字表法将所有裸鼠分为五组(n=6)。空白对照组:注射等量生理盐水,激动剂组:皮下注射TGF-β1(1微克/只),阻断剂组:腹腔注射SB431542(0.7 mg/kg),激动剂+低浓度阻断剂组:TGF-β1(1微克/只)+SB431542(0.7 mg/kg),激动剂+高浓度阻断剂组:TGF-β1(1微克/只)+SB431542(1.0 mg/kg)。饲养至24 d,统一处死并记录不同组裸鼠的肿瘤质量与体积,采用逆转录-聚合酶链反应(RTPCR)与蛋白质印迹法检测肿瘤组织中slug与E-cad基因的表达。结果使用通路激活剂激活通路后,胃癌移植瘤体积(854.00±193.00)mm^(3)高于空白对照组(544.00±60.00)mm^(3)、质量(2.74±0.52)g高于空白对照组(1.52±0.41)g、slug基因表达水平2.13±0.08高于空白对照组1.00±0.00,而激动剂组E-cad基因表达水平0.44±0.04低于空白对照组1.00±0.00(P<0.05)。结论TGF-β通路可通过增强slug蛋白表达并抑制E-cad表达,激活上皮间充质转化(EMT),提高胃癌细胞的体内增殖和侵袭能力,从而影响胃癌的进展。Objective To explore the effects of activation and blocking of transforming growth factor-β(TGF-β)pathway on the proliferation and invasion of human gastric cancer HGC-27 cells and the expressions of slug protein and epithelial cadherin(E-cad)gene.Methods From April 2021 to March 2022,human gastric cancer HGC-27 cells were used to construct a subcutaneous tumor model of 30 nude mice with gastric cancer cells,and the exogenous pathway activator TGF-β1 and blocker SB431542 were used to activate and block the TGF-βpathway.All mice were assigned into 5 groups(n=6)by random number table method.The treatment methods of each group were as follows:blank control group was injected with the same amount of normal saline,agonist group injected with TGF-β1 subcutaneously(1µg/mice),blocker groupinjected with SB431542 intraperitoneally(0.7 mg/kg),agonist+low-concentration blocker group with TGF-β1(1µg/mice)+SB431542(0.7 mg/kg),and agonist+high-concentration blocker group with TGF-β1(1µg/mice)+SB431542(1.0 mg/kg).After feeding for 24 days,the mice were killed and the tumor sizes and mass of nude mice in different groups were recorded.The expressions of slug and E-cad genes in tumor tissue were detected by reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting(WB).Results After activating the pathway with a pathway activator,the tumor size[(854.00±193.00)mm^(3) vs.(544.00±60.00)mm^(3)],the mass[(2.74±0.52)g vs.(1.52±0.41)g],and the expression level of slug protein[(2.13±0.08)vs.(1.00±0.00)]were higher than those of the control group.The expression level of E-cad gene in the agonist group[(0.44±0.04)vs.(1.00±0.00)]was lower than that in the control group(P<0.05).Conclusion TGF-βpathway can enhance the expression of slug protein and inhibit the expression of E-cad,activate epithelial-mesenchymal transition(EMT),and improve the proliferation and invasion of gastric cancer cells in vivo,thereby affecting the progression of gastric cancer.

关 键 词：胃肿瘤 转化生长因子-Β 信号通路 上皮钙黏素 SLUG 小鼠 近交BALB C 

分 类 号：R735.2[医药卫生—肿瘤]