Effects of estradiol on VEGF and bFGF by Akt in endometrial cancer cells are mediated through the NF-κB pathway

Zhang,Jieqing; Song,Honglin; Lu,Yanqiong; Chen,Haiyan; Jiang,Si; Li,Li

doi:10.3892/or.2016.4888

Effects of estradiol on VEGF and bFGF by Akt in endometrial cancer cells are mediated through the NF-κB pathway

Authors:
- Jieqing Zhang
- Honglin Song
- Yanqiong Lu
- Haiyan Chen
- Si Jiang
- Li Li
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Affiliations: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: June 21, 2016 https://doi.org/10.3892/or.2016.4888
Pages: 705-714

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Abstract

Endometrial carcinogenesis may be related to the long-term effects of estradiol with no antagonism. However, how estradiol regulates cell proliferation is unknown. In the present study, through investigating the molecular events involved in estradiol induced angiogenics factors VEGF and bFGF, we found that estradiol induced endometrial cancer cell division, proliferation, migratory and invasive capacity in vitro and upregulated mRNA expression and protein synthesis of VEGF and bFGF. The estradiol-dependent induction of the expression of VEGF and bFGF was blocked by ER inhibitor, AKT inhibitor and NF-κB inhibitor (PDTC) in estrogen receptor positive Ishikawa cells and blocked by AKT inhibitor, NF-κB inhibitor (PDTC) in estrogen receptor negative HEC-1A cells. Moreover, estradiol activation of AKT was also blocked by AKT antagonist. NF-κB activation was restricted by estradiol concentration and time. Estradiol leading to VEGF and bFGF induction was also confirmed by the development of xenograft tumors in vivo. Taken together, our data suggest that estradiol induces the production of angiogenic factors via a mechanism involving AKT-mediated NF-κB activation partly in non-genomic manner without the estrogen receptor.

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