IL-17A Promotes the Migration and Invasiveness of Cervical Cancer Cells by Coordinately Activating MMPs Expression via the p38/NF-κB Signal Pathway

被引:44
作者
Feng, Minjuan [1 ]
Wang, Yidong [1 ]
Chen, Kunlun [2 ]
Bian, Zhuoqiong [3 ]
Wu, Jinfang [1 ]
Gao, Qing [1 ]
机构
[1] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 2, Dept Obstet & Gynaecol, Xian 710049, Peoples R China
[2] Xi An Jiao Tong Univ, Sch Med, Xian 710049, Peoples R China
[3] Fifth Hosp Xian City, Dept Rheumatol 5, Xian, Peoples R China
基金
中国国家自然科学基金;
关键词
P38; MAPK; TUMOR ENVIRONMENT; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; UP-REGULATION; IN-VITRO; INHIBITORS; CARCINOMA; LIGANDS; IDENTIFICATION;
D O I
10.1371/journal.pone.0108502
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Objective: IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms. Methods: Wound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervical cancer cell migration and invasion by a panel of cervical cancer cell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-kappa B) signal pathway was detected too. Results: Here, we showed that IL-17A could promote the migration and invasion of cervical cancer cells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervical cancer cells with the pharmacological p38/NF kappa B signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A. Conclusion: IL-17A could promote the migration and invasion of cervical cancer cell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-kappa B signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervical cancer.
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页数:8
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