Abstract: 【Abstract】 Objective To study the expression of IL-8 in renal cancer and the role of IL-8 in promoting epithelial to mesenchymal transition (EMT) of renal epithelial cells. Methods ELISA was used to detect the expression of IL-8 both in renal cell carcinoma and the para-carcinoma tissue, and the morphological changes of renal carcinoma cell lines (786-0) were observed before and after IL-8 treatment. Cell invasion assay was used to evaluate the impact of IL-8 on renal cell carcinoma' invasion, and western-blot was used to detect the expression levels of E-cadherin and N-cadherin as well as the phosphorylated AKT in 786-0 cells. Results The expression of IL-8 in 20 cases of renal carcinoma was elevated when compared with the para-carcinoma tissue. After treated with IL-8, 786-0 renal carcinoma cells changed their morphology and lost their cells polarity, the expression of E-cadherin on cell surface was decreased, while the N-cadherin expression became higher. In addition, IL-8 treatment enhanced significantly 786-0 cell penetration and promoted AKT phosphorylation, while EMT caused by IL-8 stimulation was blocked by inhibiting AKT phosphorylation. Conclusion IL-8 has an ability to induce EMT of renal cell carcinoma cell lines 786-0 through activation of AKT signaling and promote the invasion of renal carcinoma cells, which may be an important mechanism for RCC metastasis.

Key words: Renal cell carcinoma, EMT, IL-8, AKT

摘要： 【摘要】 目的 研究IL-8在肾癌中的表达及其促进肾癌细胞上皮细胞-间质细胞转化(EMT)的作用机制。方法 采用ELISA检测肾癌及癌旁中IL-8的表达,观察IL-8处理前后肾癌细胞的形态结构变化;通过细胞侵袭试验观察IL-8对肾癌细胞侵袭能力的影响;采用western-blot检测IL-8刺激后肾癌细胞表面的上皮标记物(E-cadherin)和间质标志物(N-cadherin)以及细胞中磷酸化AKT的表达水平变化,抑制AKT活化后同法检测IL-8对肾癌EMT的影响。结果 20例肾癌组织标本中IL-8的表达均较癌旁组织高;IL-8刺激后786-0肾癌细胞由上皮样细胞形态向梭形转变,细胞极性消失,呈分散生长状态;同时,肾癌细胞表面的E-cadherin表达降低,而N-cadherin表达升高;IL-8处理后肾癌细胞穿透能力增强;另外,IL-8 可以促进肾癌细胞内AKT的磷酸化,抑制AKF磷酸化后可以明显抑制IL-8刺激引起的肾癌EMT改变。 结论 IL-8 可以通过AKT信号通路促进肾癌细胞EMT的发生,促进肾癌细胞的侵袭和转移,这可能是肾癌发生转移的重要机制。

关键词: 肾癌, EMT, IL-8, AKT