首页|SERPINE1在胃癌中的表达及对胃癌细胞免疫逃逸和β-catenin/N-cadherin信号通路的作用机制研究

SERPINE1在胃癌中的表达及对胃癌细胞免疫逃逸和β-catenin/N-cadherin信号通路的作用机制研究

SERPINE1 expression in gastric cancer and mechanism of immune escape and β-catenin/N-cadherin signaling pathway in gastric cancer cells

扫码查看
目的 探讨丝氨酸蛋白酶抑制剂E1(SERPINE1)在胃癌中的表达及对胃癌细胞免疫逃逸及β-连环蛋白/神经钙黏蛋白(β-catenin/N-cadherin)信号通路的作用机制.方法 选择 2020 年 1 月至 2022 年 1 月在定州市人民医院接受胃癌手术的 78 例患者作为研究对象,收集其胃癌组织及癌旁组织,采用免疫组织化学法检测组织中SERPINE1 表达情况.采用人胃癌细胞系SGC-7901 细胞,经不同处理后分为对照组(SGC-7901 细胞)、oe-SERPINE1 组(pcDNA3.1-SERPINE1 载体)、oe-NC组(空pcDNA3.1 载体)、SERPINE1 siRNA组(SERPINE1 siRNA)及si-NC组(si-NC).采用实时荧光定量PCR法检测各组细胞中SERPINE1 mRNA的表达水平,采用Transwell法检测各组细胞的侵袭数目,采用划痕实验检测各组细胞的迁移距离,采用蛋白质印迹法检测各组细胞中程序性死亡受体-1(PD-1)、程序性死亡配体-1(PD-L1)、β-catenin、N-cadherin的蛋白表达水平.结果 胃癌组织和癌旁组织中SERPINE1 阳性表达率分别为 88.46%和 19.23%,差异有统计学意义(P<0.05).oe-NC组细胞的SERPINE1 mRNA表达水平、侵袭数目、迁移距离,以及PD-1、PD-L1、β-catenin、N-cadherin蛋白表达水平与对照组差异均无统计学意义(P均>0.05).oe-SERPINE1 组细胞的上述指标均较oe-NC组显著升高(P均<0.05).si-NC组细胞的上述指标均较oe-SERPINE1 组显著降低(P均<0.05).SERPINE1 siRNA组细胞的上述指标均较si-NC组显著降低(P均<0.05).结论 SERPINE1在胃癌组织中呈高表达,下调SERPINE1 表达可显著抑制胃癌细胞的侵袭和迁移,抑制PD-1、PD-L1 表达从而阻止肿瘤细胞发生免疫逃逸,这与抑制β-catenin/N-cadherin信号通路的活性相关.
Objective This paper aims to investigate the expression of serpin peptidase inhibitor clade E member1(SERPINE1)in gastric cancer and its mechanism of action on immune escape and β-catenin/N-cadherin signaling pathway in gastric cancer cells.Methods Seventy-eight patients who underwent gastric cancer surgery at Dingzhou People's Hospital from January 2020 to January 2022 were selected as the research subjects.Their gastric cancer tissues and adjacent tissues were collected,and the expression of SERPINE1 in the tissues was detected by immunohistochemistry.The human gastric cancer cell line SGC-7901 was divided into the control group(SGC-7901 cells),the oe-SERPINE1 group(pcDNA3.1-SERPINE1 vector),the oe-NC group(empty pcDNA3.1 vector),the SERPINE1 siRNA group(SERPINE1 siRNA),and the si-NC group(si-NC)after different treatments.The real-time fluorescence quantitative PCR was used to detect the expression level of SERPINE1 mRNA in each group of cells,the Transwell method was used to detect the number of invasions in each group of cells,the scratch assay was used to detect the migration distance of each group of cells,and the Western-blotting was used to detect the protein expression levels of programmed death receptor-1(PD-1),programmed death ligand-1(PD-L1),β-catenin,and N-cadherin in each group of cells.Results The positive expression rates of SERPINE1 in gastric cancer tissue and adjacent tissues are 88.46% and 19.23%,respectively,with a statistically significant difference(P<0.05).The expression levels of SERPINE1 mRNA,invasion number,migration distance,as well as the expression levels of PD-1,PD-L1,β-catenin,and N-cadherin proteins in the oe-NC group cells show no statistically significant differences compared to those of the control group(P>0.05).The above indicators of the oe-SERPINE1 group cells are significantly higher than those of the oe-NC group(P<0.05).The above indicators of si-NC group cells are significantly lower than those of the oe-SERPINE1 group(P<0.05).The above indicators of SERPINE1 siRNA group cells are significantly reduced compared to those of the si-NC group(P<0.05).Conclusions SERPINE1 is highly expressed in gastric cancer tissues.Downregulation of SERPINE1 expression can significantly inhibit the invasion and migration of gastric cancer cells and improve the immune escape of tumor cells by inhibiting the expression of PD-1 and PD-L1,which is related to the inhibition of the activity of the β-catenin/N-cadherin signaling pathway.

Gastric cancerSerpin peptidase inhibitor clade E member1Immune escapeInvasionTransferβ-cateninN-cadherin

王峰、冯浩、李凡、宋玉涛

展开 >

073000 定州市人民医院胃肠外科

073000 定州市人民医院肝胆外科

胃癌 丝氨酸蛋白酶抑制剂E1 免疫逃逸 侵袭 迁移 β-catenin N-cadherin

河北省卫生健康委医学科学研究基金

20220437

2024

国际消化病杂志
上海市医学科学技术情报研究所

国际消化病杂志

CSTPCD
影响因子:0.796
ISSN:1673-534X
年,卷(期):2024.44(4)
  • 10