胃动蛋白2调控JAK2/STAT3通路在胃癌迁移和侵袭中的作用  

The role of Gastrokine 2 in regulating the JAK2/STAT3 pathway in the migration and invasion of gastric cancer

作　　者：周雨[1,2] 许姗 刘姣 朱亚平[1,2] 朱亚欣 李维 凌晖 Zhou Yu;Xu Shan;Liu Jiao(Shaoyang University,Shaoyang,Hunan 422000,China)

机构地区：[1]邵阳学院,湖南邵阳422000 [2]邵阳学院附属第一医院,湖南邵阳422000 [3]肿瘤细胞与分子病理学湖南省高校重点实验室,南华大学衡阳医学院肿瘤研究所,湖南衡阳421001

出　　处：《湘南学院学报（医学版）》2024年第2期1-7,共7页Journal of Xiangnan University（Medical Sciences）

基　　金：湖南省科技厅临床医学技术创新指导项目(2018SK51901);湖南省教育厅科研项目(21B0693)。

摘　　要：目的 阐明胃动蛋白2(gastrokine 2,GKN2)在人胃癌中的作用及相关分子机制。方法 采用免疫组织化学技术检测90例胃癌(gastric cancer,GC)组织、48例癌旁胃组织(adjacent tissue,PT)和22例远端胃黏膜组织(distal gastric mucosa,DGM)中GKN2和TFF1的表达;构建GKN2基因高表达载体,转染人胃癌细胞MKN28和SGC7901,qRT-PCR和Western blot验证转染效率,实验分为3组:GKN2组、NC组、空白组。采用CCK-8、Transwell迁移和侵袭实验测定细胞增殖、迁移和侵袭能力;Western blot观察GKN2转染后JAK2、STAT3、p-JAK2、p-STAT3蛋白表达变化。结果 与癌旁胃组织(GKN2,43.75%;TFF1,62.50%)和远端胃黏膜组织(GKN2,86.36%;TFF1,81.82%)相比,胃癌组织中GKN2(6.67%)、TFF1(21.11%)表达下调(P<0.05);但胃癌组织中GKN2与TFF1的表达无相关性(r≈0.23,P=0.074)。与NC组(0.25±0.03)和空白组(0.24±0.03)相比,GKN2转染MKN28细胞24 h后OD570下降至(0.15±0.02),GKN2转染48 h后的OD570(0.22±0.06)也低于相应的NC组(0.49±0.06)和空白组(0.44±0.02),72 h后的OD570(0.25±0.05)比相应的NC组(0.65±0.21)和空白组(0.63±0.03)减少(P<0.05);SGC7901细胞中GKN2转染24 h后OD570(0.721±0.014)低于NC组(1.352±0.168)和空白组(1.381±0.168),48 h后的OD570(0.674±0.028)也低于相应的NC组(1.459±0.211)和空白组(1.565±0.351),72 h后GKN2的OD570(0.400±0.028)比NC组(1.745±0.194)和空白组(1.792±0.385)减少(P<0.05)。Transwell迁移实验发现,MKN28细胞中GKN2转染组穿过膜的癌细胞数(26±5.01)明显低于NC组(109±7.10)和空白组(110±4.04)(P<0.05);与NC组(94±6.00)和空白组(75+7.05)相比,SGC7901中GKN2高表达显著降低了穿过膜的细胞数(37±3.11)(P<0.05)。Transwell侵袭实验证实,与NC组(67±5.02)和空白组(66±5.16)相比,GKN2高表达显著降低了穿过基质胶的MKN28细胞数(28±4.10)(P<0.05);SGC7901细胞中GKN2转染组穿过基质胶的癌细胞数(10±2.06)远低于NC组(58±5.13)和空白组(55±3.17)(P<0.05)。Western blot结果显示,GKN2高表达�Objective To investigate the role of Gastrokine 2(GKN2)in gastric cancer(GC)and its associated molecular mechanisms.Methods Immunohistochemistry was used to detect the expression of GKN2 and TFF1 in 90 gastric cancer tissues(GC),48 adjacent gastric tissues(PT),and 22 distal gastric mucosa tissues(DGM).A GKN2 overexpression vector was constructed and transfected into human gastric cancer cells MKN28 and SGC7901.Transfection efficiency was validated by qRT-PCR and Western blot.The experiment included three groups:GKN2 group,NC group,and blank group.CCK-8,transwell migration and invasion assays were used to determine the cell proliferation,migration,and invasion abilities,and Western blot was employed to observe changes in JAK2,STAT3,p-JAK2,and p-STAT3 protein expression after GKN2 transfection.Results The expression of GKN2(6.67%)and TFF1(21.11%)was down-regulated in gastric cancer tissues(P<0.05)compared with paracancerous gastric tissues(GKN2,43.75%;TFF1,62.50%)and distal gastric mucosal tissues(GKN2,86.36%;TFF1,81.82%);however,there was no correlation between GKN2 and TFF1 expression in gastric cancer tissues(r≈0.23,P=0.074).Compared with the NC group(0.25±0.03)and the blank group(0.24±0.03),the OD570 of GKN2-transfected MKN28 cells decreased to(0.15±0.02)after 24 h,and the OD570 of GKN2-transfected MKN28 cells(0.22±0.06)after 48 h was also lower than the corresponding OD570 of the NC group(0.49±0.06)and the blank group(0.44±0.02)at 72 h(P<0.05),and OD570(0.25±0.05)after 72 h was reduced(P<0.05)compared with the corresponding NC group(0.65±0.21)and blank group(0.63±0.03).OD570(0.721±0.014)after 24 h of GKN2 transfection in SGC7901 cells was lower than that in the NC group(1.352±0.168)and blank group(1.381±0.168),and OD570(0.674±0.028)after 48 h was also lower than that of the corresponding NC group(1.459±0.211)and blank group(1.565±0.351),and the OD570 of GKN2 after 72 h was lower than that of the NC group(1.745±0.194)and blank group(1.792±0.385)decreased(P<0.05).Transwell migration assay reve

关 键 词：胃癌 胃动蛋白2 JAK2/STAT3通路 迁移 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]