PIAS1调控炎症微环境诱导的胃癌上皮-间质转化的实验研究  

Effect of PIAS1 on Epithelial-mesenchymal Transition of Gastric Cancer under Inflammatory Microenvironment

作　　者：陈平[1] 王唯一[1] 周郁芬[1] 谢玲[1] 章永平[1] 吴云林[1] CHEN Ping WANG Weiyi ZHOU Yufen XIE Ling ZHANG Yongping WU Yunlin(Department of Gastroenterology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai （201801)

机构地区：[1]上海交通大学医学院附属瑞金医院北院消化内科,201801

出　　处：《胃肠病学》2017年第1期15-19,共5页Chinese Journal of Gastroenterology

摘　　要：背景:作为炎症网络调控的重要介质,STAT活化抑制蛋白1(PIAS1)在胃癌组织中低表达,并与疾病进展相关,但具体机制还有待研究。目的:探讨PIAS1对炎症微环境下胃癌上皮-间质转化(EMT)的影响。方法:构建重组腺病毒Ad5/F35-PIAS1和Ad5/F35-null并转染胃癌细胞株SGC-7901,以RT-PCR法和蛋白质印迹法分别验证PIAS1 mRNA和蛋白表达。随后将SGC-7901细胞分为IL-6治疗组、Ad5/F35-PIAS1+IL-6治疗组、Ad5/F35-null+IL-6治疗组,以MTT法测定细胞增殖率,细胞划痕实验和Transwell侵袭实验测定细胞迁移和侵袭能力,蛋白质印迹法测定E-cadherin、Snail、Twist、Vimentin、P-p38MAPK蛋白表达。结果:转染Ad5/F35-PIAS1可明显上调SGC-7901细胞中PIAS1 mRNA和蛋白表达。与IL-6治疗组和Ad5/F35-null+IL-6治疗组相比,Ad5/F35-PIAS1+IL-6治疗组细胞增殖率、细胞迁移和侵袭能力均显著下降(P<0.01),Snail、Twist、Vimentin、P-p38MAPK蛋白表达显著降低(P<0.01),E-cadherin蛋白表达显著增高(P<0.01)。而IL-6治疗组和Ad5/F35-null+IL-6治疗组上述指标相比差异均无统计学意义(P>0.05)。结论:PIAS1可抑制胃癌细胞在炎症微环境下发生的EMT,进而可能在抑制肿瘤侵袭与转移的过程中发挥重要作用。Background： Protein inhibitor of activated STAT 1 （PIAS1） is an important regulator for inflammatory signaling network, which is low expressed in gastric cancer and associated with development of cancer, but its mechanism has not been elucidated. Aims： To investigate the effect of PIAS1 on epithelial-mesenchymal transition （EMT） of gastric cancer under inflammatory microenvironment. Methods： Recombinant adenovirus AdS/F35-PIAS1 and AdS/F35-null were constructed and transfected into gastric cancer cell line SGC-7901, mRNA and protein expressions of PIAS1 were detected by RT-PCR and Western blotting, respectively. SGC-7901 ceils were divided into IL-6 treatment group, AdS/F35-PIAS1 ＋ IL-6 treatment group and AdS/F35-null ＋ IL-6 treatment group. Cell proliferation was measured by MTF method, migration and invasion capacities were assessed by wound healing test and Transwell chamber invasion assay. Protein expressions of E-cadherin, Snail, Twist, Vimentin and P-p38MAPK were assessed by Western blotting. Results： The transfection of AdS/F35-PIAS1 significantly increased the expressions of PIAS1 mRNA and protein in SGC-7901 cells. Compared with IL- 6 treatment group and AdS/F35-null ＋ IL-6 treatment group, capacities of cell proliferation, migration and invasion were significantly decreased （P 〈 0.01 ）; protein expressions of Snail, Twist, Vimentin and P-p38MAPK were significantly decreased while expression of E-cadherin protein was significantly increased in AdS/F35-PIAS1 ＋ IL-6 treatment group （ P 〈 0. O1 ）. No significant differences in above-mentioned indices were found between IL-6 treatment group and AdS/F35- null ＋ IL-6 treatment group （ P 〉 0.05 ）. Conclusions： PIAS1 could inhibit EMT of gastric cancer cells under inflammatorymicroenvironment, and may play an important role in inhibition of tumor invasion and metastasis.

关 键 词：胃肿瘤 上皮-间质转化 炎症微环境 活化STAT的蛋白抑制物 白细胞介素6 

分 类 号：R735.2[医药卫生—肿瘤]