title: 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.
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Department of Gynecology and Obstetrics, Bao'an Maternal and Child Health Hospital, Shenzhen, China.
authors: Xue-Feng
authors: XF
authors: Ma
authors: Department of Gynecology and Obstetrics, Bao'an Maternal and Child Health Hospital, Shenzhen, China.
authors: Jie
authors: J
authors: Zhang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors: Han-Lin
authors: HL
authors: Shuai
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors: Bao-Zhang
authors: BZ
authors: Guan
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors: Xin
authors: X
authors: Luo
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address: yanrljnu@163.com.
authors: Rui-Ling
authors: RL
authors: Yan
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D045744:Cell Line, Tumor; D002465:Cell Movement; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010636:Phenols / Q000633:toxicity*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D005353:Fibronectins; D051550:I-kappa B Kinase; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D010636:Phenols; D011493:Protein Kinase C; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Cervical cancer; Migration; NF-κB