Yang Zhiping, Gao Xin, Wang Jingyu, Xu Longsheng, Zheng Ying, Xu Yufen
Department of Oncology (04-F-14), The First Affiliated Hospital of Jiaxing University, Jiaxing.
Department of Oncology, Suzhou Municipal Hospital of Nanjing Medical University, Suzhou.
Onco Targets Ther. 2018 Feb 16;11:843-849. doi: 10.2147/OTT.S155905. eCollection 2018.
Interleukin-33 (IL-33), belonging to IL-1 family cytokines, has been reported to participate in cancer growth and metastasis. The clinical values of IL-33 in lung cancer have been previously investigated. We aimed to elucidate the probable role of IL-33 in the migration and invasion of lung cancer cells.
Cell migration and invasiveness were tested by Transwell assay. Western blotting analysis was performed to detect protein expression.
We found that IL-33 treatment in human lung A549 cells dose-dependently enhanced their migratory and invasive ability, accompanied by elevated expression of matrix metallo-proteinase (MMP) 2 and MMP9. Meanwhile, IL-33-induced cell migration and invasion were significantly abolished by small interfering RNA-targeting ST2, the specific receptor of IL-33. Furthermore, IL-33 exposure induced the phosphorylation of AKT. Pretreatment with an AKT inhibitor LY294002 markedly attenuated IL-33-induced cell migration and invasion.
IL-33/ST2 promoted the migration and invasiveness of lung cancer cells through AKT pathway. Our findings strongly suggest that IL-33 may serve as a promising therapeutic strategy for lung cancer.
白细胞介素-33(IL-33)属于白细胞介素-1家族细胞因子,据报道参与癌症的生长和转移。此前已对IL-33在肺癌中的临床价值进行了研究。我们旨在阐明IL-33在肺癌细胞迁移和侵袭中可能发挥的作用。
采用Transwell试验检测细胞迁移和侵袭能力。进行蛋白质印迹分析以检测蛋白表达。
我们发现,用IL-33处理人肺A549细胞可剂量依赖性地增强其迁移和侵袭能力,同时基质金属蛋白酶(MMP)2和MMP9的表达升高。同时,靶向IL-33特异性受体ST2的小干扰RNA可显著消除IL-33诱导的细胞迁移和侵袭。此外,暴露于IL-33可诱导AKT磷酸化。用AKT抑制剂LY294002预处理可显著减弱IL-33诱导的细胞迁移和侵袭。
IL-33/ST2通过AKT途径促进肺癌细胞的迁移和侵袭。我们的研究结果强烈表明,IL-33可能是一种有前景的肺癌治疗策略。