IL-23促进食管鳞状细胞癌细胞上皮间质转化和迁移

［摘要］目的: 探讨外源性IL-23通过PI3K/AKT/c-Myc通路对TE-1细胞上皮间质转化(epithelial-mesenchymal transition，EMT)和迁移的影响。方法: 采用免疫组织化学和免疫荧光检测12例食管鳞状细胞癌(esophageal squamous cell carcinoma，ESCC)患者癌组织与配对癌旁组织中IL 23及其受体(IL 23R)的表达和胞内定位；蛋白质印迹检测TE 1细胞与阴性对照NIH3T3细胞中IL-23p19表达，流式细胞术检测IL-23R的表达；PCR和蛋白质印迹法检测空白对照组，50 ng/mL IL-23组，1 μmol/L Wortmannin +50 ng/mL IL-23组细胞中c-Myc mRNA及其蛋白与E 钙黏蛋白、波形蛋白、p-AKT、Snail 1、Slug蛋白的表达；划痕和Transwell实验检测各组TE-1细胞侵袭和迁移能力。结果： 与癌旁组织比较，ESCC组织及其细胞质中IL-23呈高表达，细胞膜上IL-23R高表达；与阴性对照比较，TE 1细胞中IL-23p19及IL-23R呈过表达（P均<0.01）；与对照组比较，IL-23组细胞中c-Myc mRNA及其蛋白、p-AKT、波形蛋白、Snail 1、Slug蛋白明显升高，E 钙黏蛋白表达明显降低，TE-1细胞划痕愈合率和迁移数明显升高(P均<0.05)。与IL-23组比较，IL-23+Wortmannin组细胞中c Myc mRNA及其蛋白、p-AKT、波形蛋白、Snail 1、Slug蛋白明显降低，E-钙黏蛋白明显升高，TE-1细胞划痕愈合率和迁移数明显降低(P均<0.05)。结论： IL-23通过PI3K/AKT/c-Myc通路促进食管鳞癌细胞上皮间质转化和迁移。

IL-23 strengthened epithelial mesenchymal transition and migration of esophageal squamous carcinoma cells

Abstract]Objective: To explore the effect of exogenous IL-23 through PI3K/AKT/c Myc pathway on the epithelial mesenchymal transition (EMT) and migration of esophageal squamous carcinoma cells. Methods: The expression and localization of IL-23 and interleukin 23 receptor (IL 23R) in tumor and adjacent normal tissues from 12 esophageal squamous cell carcinoma (ESCC) patients were detected by immunohistochemistry and immunofluorescence; IL-23p19 and IL-23R expression in TE-1 cells and NIH3T3 cells was detected by Western blotting and flow cytometry respectively; PCR and Western blotting were used to examine the expression of c-Myc mRNA and c-Myc,E-cadherin,Vimentin,p-AKT,Snail 1,Slug protein in control group, 50 ng/mL IL 23 group, and 1 μmol/L Wortmannin +50 ng/mL IL-23 group in TE-1 cells; and the invasion and migration of IL-23 treated TE 1 cells was evaluated by Transwell assay and wound healing assay. Results: Compared with adjacent normal tissues, IL-23 highly expressed in ESCC tissues and cytoplasm, and IL-23R also expressed on the cell membrane. Compared with negative control NIH3T3 cells, IL-23p19 and IL-23R were showed higher expression levels in TE 1 cells(P<0.01). Compared with control group, the expression of c-Myc mRNA, c-Myc, p-AKT, Vimentin, Snail 1, Slug protein levels were up regulated, E-cadherin protein was down-regulated, the rate of cell wound healing and the migration were significantly increased in IL 23 group (all P<0.05). Compared with IL-23 alone group, the expression of c-Myc mRNA and c-Myc, p-AKT, Vimentin, Snail 1, Slug protein levels were down regulated, E-cadherin protein was up-regulated, the rate of cell wound healing and the transfer ability were significantly reduced in IL-23+ Wortmannin group (all P<0.05). Conclusion: IL-23 strengthened EMT and migration of esophageal squamous carcinoma cells via PI3K/AKT/c Myc pathway.