IFITM1在胰腺癌中的表达及对胰腺癌细胞生物学行为的影响  

Expression of IFITM1 in pancreatic cancer and its effect on biological behaviors of pancreatic cancer cells

作　　者：赵秀雷[1] 张雷[1] 刘汝海[1] 李凤山[1] 张执全[1] 孔德帅[1] 张耀敏 石倩倩 刘婷婷 ZHAO Xiulei;ZHANG Lei;LIU Ruhai;LI Fengshan;ZHANG Zhiquan;KONG Deshuai;ZHANG Yaomin;SHI Qianqian;LIU Tingting(The First Department of Hepatobiliary and Pancreatic Surgery,Cangzhou Central Hospital,Cangzhou,Hebei 061000,China)

机构地区：[1]河北省沧州市中心医院肝胆胰外一科,河北沧州061000

出　　处：《中国普通外科杂志》2022年第3期351-358,共8页China Journal of General Surgery

基　　金：河北省医学科学研究课题基金资助项目(20210591)。

摘　　要：背景与目的:干扰素诱导的跨膜蛋白1(IFITM1)是一种在淋巴细胞中转导同型黏附信号的膜复合物,在胰腺癌组织中表达量异常,但是其在胰腺癌中的作用机制则仍不清楚,因此,本研究初步探讨IFITM1的表达对胰腺癌细胞生物学行为的影响。方法:用Western blot法检测78例胰腺癌患者(32例转移,46例未转移)的癌组织和癌旁正常组织中IFITM1的表达。将胰腺癌PANC-1细胞转染IFITM1过表达质粒(IFITM1组)或转染IFITM1过表达质粒同时添加ERK_(1/2)通路抑制剂LY3214996(IFITM1+LY3214996组)后,以无处理的PANC-1细胞为对照组,分别用检测Western blot、CCK-8实验、流式细胞术、划痕愈合实验、Transwell实验检测IFITM1蛋白与ERK_(1/2)蛋白磷酸化水平(ERK_(1/2)/p-ERK_(1/2))、细胞增殖活力、凋亡以及迁移与侵袭能力的变化。结果:IFITM1蛋白相对表达量在胰腺癌组织中明显高于癌旁正常组织,在有转移的胰腺癌组织中明显高于无转移的胰腺癌组织(均P<0.05)。与对照组PANC-1细胞比较,IFITM1组PANC-1细胞的IFITM1蛋白表达水平、ERK_(1/2)/p-ERK_(1/2)水平明显升高,凋亡率明显降低,细胞增殖活力、迁移与侵袭能力均明显增强(均P<0.05);IFITM1+LY3214996组PANC-1细胞除IFITM1蛋白表达水平明显升高外(P<0.05),其余指标均无明显变化(均P>0.05)。结论:IFITM1在胰腺癌组织中表达上调,且与胰腺癌的恶性生物学行为密切相关,其作用机制可能是通过磷酸化激活ERK_(1/2)路调控胰腺癌细胞的生长、迁移和侵袭能力有关。Background and Aims:Interferon-induced transmembrane protein 1(IFITM1),a membrane complex transducing homotypic adhesion signals in lymphocytes,is abnormally expressed in pancreatic cancer tissues,but its action mechanism in pancreatic cancer remains unclear.Therefore,this study was conducted as a preliminary investigation to examine the influences of the expression of IFITM1 on biological behaviors of pancreatic cancer cells.Methods:The expressions of IFITM1 in the surgical specimens of cancer tissue and adjacent normal tissue from 78 pancreatic cancer patients(32 cases having metastasis,46 cases not having metastasis)were determined by Western blot analysis.In pancreatic cancer PANC-1 cells after transfection with IFITM1-overxpression plasmids alone(IFITM1 group)or with simultaneous addition of ERK_(1/2)pathway inhibitor LY3214996(IFITM1+LY3214996 group),with untreated PANC-1 cells as control group,the changes in levels of IFITM1 protein and ERK_(1/2)protein phosphorylation(ERK_(1/2)/p-ERK_(1/2)),proliferative viability and apoptosis as well as migration and invasion abilities were determined by Western blot,CCK-8 assay,flow cytometry,Scratch healing assay and Transwell assay,respectively.Results:The relative expression level of IFITM1 protein in pancreatic cancer tissue was significantly higher than that in adjacent normal tissue,and in pancreatic cancer tissue with metastasis was higher than that in pancreatic cancer tissue without metastasis(both P<0.05).Compared with PANC-1 cells in control group,the PANC-1 cells in IFITM1 group showed significantly increased IFITM1 protein and ERK_(1/2)/p-ERK_(1/2)levels,decreased apoptosis rate,increased proliferative viability and enhanced migration and invasion abilities(all P<0.05);except the up-regulated IFITM1 protein level(P<0.05),the PANC-1 cells in IFITM1+LY3214996 group showed no significant changes in all other studied parameters(all P>0.05)Conclusion:IFITM1 expression is increased in pancreatic cancer tissue,which is closely related to the malignant behaviors o

关 键 词：胰腺肿瘤 干扰素诱导的跨膜蛋白1 细胞增殖 肿瘤侵润 

分 类 号：R735.9[医药卫生—肿瘤]