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白细胞介素-33增强了人肺癌细胞的迁移和侵袭能力。

Interleukin-33 enhanced the migration and invasiveness of human lung cancer cells.

作者信息

Yang Zhiping, Gao Xin, Wang Jingyu, Xu Longsheng, Zheng Ying, Xu Yufen

机构信息

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.

出版信息

Onco Targets Ther. 2018 Feb 16;11:843-849. doi: 10.2147/OTT.S155905. eCollection 2018.

Abstract

AIM

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.

METHODS

Cell migration and invasiveness were tested by Transwell assay. Western blotting analysis was performed to detect protein expression.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c1/5820469/5f8027c8e4aa/ott-11-843Fig1.jpg

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