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Introduction
Epithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancer cases, and is one of the three most common gynecological malignancies (1). EOC has a poor prognosis and is the leading cause of death from gynecologic cancers. Although advanced surgical techniques and newly emerging targeted therapies have improved patient outcomes, the 5-year survival rate for EOC patients is still low, at approximately 30–40% (2,3). In addition, the precise molecular mechanisms underlying the biological behavior of EOC remain unclear. Several hypotheses have been proposed to explain the etiology of EOC, such as the incessant ovulation hypothesis (4), the gonadotropin theory (5) and the sex-steroid hormone hypothesis (6). Increasing basic and epidemiological evidence has shown that the enriched hormonal environment in the ovary can influence the development of EOC (7).
Gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), are conducive to the growth of ovarian cancer based on the ‘gonadotropin theory’ (5) and are regulated by gonadotropin-releasing hormone (GnRH). GnRH agonists initially stimulate the release of gonadotropins, while sustained administration inhibits the release by desensitizing or downregulating the expression of the GnRH receptor (GnRHR). Clinically, GnRH agonists have been widely used in the treatment of hormone-dependent tumors, such as breast (8) and prostate cancer (9). GnRH and GnRH agonists are involved in the regulation of proliferation, apoptosis and other biological behaviors of ovarian cancer cells (10,11). Previous studies, including ours, have revealed that GnRH agonists inhibit the growth and proliferation of ovarian cancer through GnRHR (10,12–14), indicating that GnRH agonists and the GnRHR may be used as antitumor strategies in the future (15).
However, the effect of GnRH agonists on the apoptosis of EOC cells and their molecular mechanisms remain largely unidentified. In this study, we aimed to investigate the biological function of goserelin and the underlying mechanisms involving goserelin and EOC apoptosis using in vitro and in vivo experiments. The present study will facilitate a better understanding of the mechanisms underlying the effect of GnRH agonists on EOC. Meanwhile, key factors in the regulatory pathways may provide new therapeutic targets for the treatment of EOC.
Materials and methods
Cell lines and reagents
The human EOC cell lines (SKOV3, SKOV3-ip and A2780) were kindly provided by the University of Texas MD Anderson Cancer...