Goserelin promotes the apoptosis of epithelial ovarian cancer cells by upregulating forkhead box O1 through the PI3K/AKT signaling pathway

Zhang,Ning; Qiu,Junjun; Zheng,Tingting; Zhang,Xiaodan; Hua,Keqin; Zhang,Ying

doi:10.3892/or.2017.6159

Goserelin promotes the apoptosis of epithelial ovarian cancer cells by upregulating forkhead box O1 through the PI3K/AKT signaling pathway

Authors:
- Ning Zhang
- Junjun Qiu
- Tingting Zheng
- Xiaodan Zhang
- Keqin Hua
- Ying Zhang
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Affiliations: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China
Published online on: December 15, 2017 https://doi.org/10.3892/or.2017.6159
Pages: 1034-1042
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), are conducive to the growth of ovarian cancer based on the ‘gonadotropin theory’ and are regulated by gonadotropin-releasing hormone (GnRH). The present study was carried out to investigate the effect of goserelin, a GnRH agonist, on the apoptosis of epithelial ovarian cancer (EOC) cells and the underlying in vitro and in vivo mechanisms. Through flow cytometry, Hoechst staining and TUNEL staining, we demonstrated that goserelin promoted the apoptosis of EOC cells both in vitro and in vivo. Through human apoptosis gene PCR array, we verified that the promotion of EOC cell apoptosis by goserelin was linked to the upregulation of members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, which have been identified as downstream targets of forkhead box O1 (FOXO1). Goserelin enhanced FOXO1 expression, and siRNA-mediated knockdown of FOXO1 abrogated the induction of apoptosis by goserelin. Moreover, goserelin decreased AKT activity, and FOXO1 upregulation by goserelin was dependent on the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In vivo, the expression of key factors in the PI3K/AKT/FOXO1 pathway was consistent with that observed in vitro. In conclusion, our data suggested that goserelin may promote EOC cell apoptosis by upregulating FOXO1 through the PI3K/AKT signaling pathway. We believe that GnRH agonists may be potential antitumor agents, and key factors in the PI3K/AKT-FOXO1 pathway may also be novel therapeutic targets for the treatment of EOC.

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