Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway

被引:73
|
作者
Li, Xiaozhao [1 ,5 ]
Bao, Chunyu [2 ]
Ma, Zhinan [3 ]
Xu, Boqun [1 ,4 ]
Ying, Xiaoyan [1 ,4 ]
Liu, Xiaoqiu [6 ,7 ]
Zhang, Xuesen [5 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Matern & Child Hlth Hosp, Dept Obstet & Gynecol, Nanjing, Jiangsu, Peoples R China
[3] Yangzhou Univ, Coll Med, Yangzhou Maternal & Child Hlth Hosp, Dept Obstet & Gynecol, Yangzhou, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Sir Run Hosp, Dept Obstet & Gynecol, Nanjing, Jiangsu, Peoples R China
[5] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Key Lab Pathogen Biol Jiangsu Prov, Nanjing, Jiangsu, Peoples R China
[7] Nanjing Med Univ, Dept Microbiol, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Ovarian cancer; PFOA; MMP-2/-9; ERK/NF-kappa B; Migration and invasion; NF-KAPPA-B; MATRIX METALLOPROTEINASE-2/-9 EXPRESSION; SIGNAL-REGULATED KINASE; ENVIRONMENTAL-POLLUTANTS; UP-REGULATION; MMP-9; PROGRESSION; EXPOSURE; INVASIVENESS; CARBOPLATIN;
D O I
10.1016/j.toxlet.2018.05.009
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (>= 100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration. Notably, PFOA treatment induced activation of ERK1/2/ NF-kappa B signaling. Pre-treatment with U0126, an ERK1/2inhibitor; or JSH-23, a NF-kappa B inhibitor, can reverse the PFOA-induced cell migration and invasion. Consistent with these results, inhibiting ERK1/2 or NF-kappa B signaling abolished PFOA-induced up-regulation of MMP-2/-9 expression. These results indicate that PFOA can stimulate ovarian cancer cell migration, invasion and MMP-2/-9 expression by up-regulating ERK/NF-kappa B pathway.
引用
收藏
页码:44 / 50
页数:7
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