IRE1α调控CD155表达影响NK细胞对结肠癌细胞的杀伤敏感性  

The expression of IRE1α regulatory CD155 affects the killing sensitivity of NK cells to colon cancer cells

作　　者：李会敏[1] 夏兴洲[1] 王世超[1] 王小星 王文真 黄真婷 于政洋 LI Huimin;XIA Xingzhou;WANG Shichao;WANG Xiaoxing;WANG Wenzhen;HUANG Zhenting;YU Zhengyang(Department of Gastroenterology,the Fifth Affiliated Hospital of Zhengzhou University,Henan Zhengzhou 450000,China)

机构地区：[1]郑州大学第五附属医院消化内科,河南郑州450000

出　　处：《现代肿瘤医学》2022年第7期1190-1195,共6页Journal of Modern Oncology

基　　金：河南省医学科技攻关计划项目(编号:201802165)。

摘　　要：目的:探讨肌醇的跨膜激酶/核酸内切酶1α(inositol-requiring transmembrane kinase/endonuclease 1α,IRE1α)调控CD155表达对自然杀伤(nature killer,NK)细胞杀伤结肠癌细胞作用的影响。方法:免疫组织化学法检测结肠癌组织及癌旁组织中IRE1α的表达;qRT-PCR与Western blot检测IRE1α与CD155的mRNA及蛋白表达;流式细胞术检测人外周血CD3^(-)CD56^(+)NK细胞百分比及与其纯度和NK细胞表面T细胞免疫球蛋白和ITIM结构域蛋白(T cell immunoreceptor with Ig and ITIM domains,TIGIT)的表达;乳酸脱氢酶释放法检测NK细胞对结肠癌细胞的杀伤率。结果:IRE1α在结肠癌组织和细胞中的表达高于癌旁组织及人正常结肠上皮细胞;结肠癌患者外周血CD3^(-)CD56^(+)NK细胞百分比低于健康者。si-IRE1α组结肠癌细胞的IRE1α表达水平低于si-NC组(P<0.05),CD155表达水平高于si-NC组(P<0.05),NK细胞对si-IRE1α组结肠癌细胞的杀伤率高于si-NC组的杀伤率(P<0.05),NK细胞对si-IRE1α+TIGIT-mcAb组结肠癌细胞的杀伤率高于si-IRE1α组的杀伤率(P<0.05)。Pc-IRE1α组结肠癌细胞的IRE1α表达水平高于Pc组(P<0.05),CD155表达水平低于Pc组(P<0.05),NK细胞对Pc-IRE1α组结肠癌细胞的杀伤率低于Pc组的杀伤率(P<0.05)。Pc-IRE1α+si-CD155组结肠癌细胞CD155表达水平高于Pc-IRE1α+si-NC组(P<0.05),NK细胞对Pc-IRE1α+si-CD155组结肠癌细胞的杀伤率高于Pc-IRE1α+si-NC组(P<0.05),NK细胞对Pc-IRE1α+si-CD155+TIGIT-mcAb组细胞的杀伤率高于Pc-IRE1α+si-CD155组(P<0.05)。结论:结肠癌组织和细胞中IRE1α高表达,IRE1α负调控结肠癌细胞CD155的表达,影响NK细胞对结肠癌细胞的杀伤敏感性。Objective:To investigate the effect of IRE1α regulating the expression of CD155 on the killing of colon cancer cells by NK cells.Methods:Immunohistochemistry was used to detect the expression of IRE1αin colon cancer tissues and adjacent tissues to the cancer.qRT-PCR and Western blot were performed to detect the mRNA and protein expression of IRE1α and CD155.Flow cytometry was utilized to evaluate the percentage and purity of CD3^(-)CD56^(+)NK cells in human peripheral blood NK cells and the expression of TIGIT in NK cells.LDH releasing assay was used to detect cytotoxicity of NK cells against colon cancer cells.Results:The expression of IRE1α in colon cancer tissues and cells was higher than that in adjacent tissues and human normal colon epithelial cells.The percentage of CD3^(-)CD56^(+)NK cells in peripheral blood of colon cancer patients was lower than that of healthy people.The expression level of IRE1α in colon cancer cells in the si-IRE1α group was lower than that in the si-NC group(P<0.05),and the expression level of CD155 was higher than that in the si-NC group(P<0.05),the killing rate of NK cells on colon cancer cells in the si-IRE1α group was higher than that in the si-NC group(P<0.05),and the killing rate of NK cells on colon cancer cells in the si-IRE1α+TIGIT-mcAb group was higher than that of si-IRE1α group killing rate(P<0.05).The expression level of IRE1α in colon cancer cells in the Pc-IRE1α group was higher than that in the Pc group(P<0.05),and the expression level of CD155 was lower than that in the Pc group(P<0.05),the killing rate of NK cells to colon cancer cells in the Pc-IRE1α group was lower than that of the Pc group(P<0.05).The expression level of CD155 in colon cancer cells in the Pc-IRE1α+si-CD155 group was higher than that in the Pc-IRE1α+si-NC group(P<0.05),the killing rate of NK cells to colon cancer cells in the Pc-IRE1α+si-CD155 group was higher than that in the Pc-IRE1α+si-NC group(P<0.05),and the killing rate of NK cells to the Pc-IRE1α+si-CD155+TIGIT-mcAb group

关 键 词：IRE1α CD155 NK细胞 结肠癌 

分 类 号：R735.3[医药卫生—肿瘤]