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IKKβ/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells.

Abstract
Cervical cancer is considered as the second most common female malignant disease. There is an urgent need to illustrate risk factors which can trigger the motility of cervical cancer cells. Our present study revealed that nanomolar concentration of bisphenol A (BPA) significantly promoted the in vitro migration and invasion of cervical cancer HeLa, SiHa, and C-33A cells. Further, BPA treatment increased the expression of metalloproteinase-9 (MMP-9) and fibronectin (FN) in both HeLa and SiHa cells, while did not obviously change the expression of MMP-2, vimentin (Vim) or N-Cadherin (N-Cad). BAY 11-7082, the inhibitor of NF-κB, significantly abolished BPA induced up regulation of FN and MMP-9 in cervical cancer cells. While the inhibitors of PKA (H89), ERK1/2 (PD 98059), EGFR (AG1478), or PI3K/Akt (LY294002) had no effect on the expression of either FN or MMP-9. BPA treatment rapidly increased the phosphorylation of both IκBα and p65, stimulated nuclear translocation, and up regulated the promoter activities of NF-κB. The BPA induced up regulation of MMP-9 and FN and activation of NF-κB were mediated by phosphorylation of IKKβ via PKC signals. Collectively, our study found for the first time that BPA stimulated the cervical cancer migration via IKK-β/NF-κB signals.
AuthorsXue-Feng Ma, Jie Zhang, Han-Lin Shuai, Bao-Zhang Guan, Xin Luo, Rui-Ling Yan
JournalArchives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 573 Pg. 52-8 (May 01 2015) ISSN: 1096-0384 [Electronic] United States
PMID25797437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Fibronectins
  • NF-kappa B
  • Phenols
  • I-kappa B Kinase
  • Protein Kinase C
  • Matrix Metalloproteinase 9
  • bisphenol A
Topics
  • Benzhydryl Compounds (toxicity)
  • Cell Line, Tumor
  • Cell Movement
  • Endocrine Disruptors (toxicity)
  • Female
  • Fibronectins (metabolism)
  • Humans
  • I-kappa B Kinase (metabolism)
  • Matrix Metalloproteinase 9 (metabolism)
  • NF-kappa B (metabolism)
  • Neoplasm Invasiveness
  • Phenols (toxicity)
  • Phosphorylation
  • Protein Kinase C (metabolism)
  • Signal Transduction
  • Uterine Cervical Neoplasms (pathology)

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