Goserelin can inhibit ovarian cancer proliferation and simultaneously protect ovarian function from cisplatin: anin vitroandin vivostudy

Abstract

This study investigates whether goserelin can inhibit ovarian cancer proliferation and protect ovarian function from cisplatin (CDDP). We evaluated proliferation and AKT phosphorylation in goserelin-treated ES-2 and SKOV3-ip ovarian cancer cells. Anti-Müllerian hormone (AMH) in human granulosa cells (hGCs) cotreated with goserelin and CDDP was measured by ELISA. Tumour volumes, Ki-67 expression, estrus, follicles, ovarian volumes, and serum AMH were compared in nude mice bearing transplanted tumours treated with goserelin and/or CDDP. Our results showed that goserelin inhibited cellular proliferation and AKT phosphorylation in vitro, and inhibited tumour growth and Ki-67 expression in vivo. Goserelin and CDDP cotreatment decreased the estrus cycles of the nude mice and prolonged estrus duration. Goserelin abrogated the CDDP-induced down-regulation of primary and preantral follicle percentage and ovarian volume. Goserelin increased AMH secretion in vitro and in vivo. In conclusion, goserelin inhibited ovarian cancer proliferation and simultaneously protected ovarian function from CDDP.

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

“…Theoretically, GnRH agonists inhibit the growth and proliferation of ovarian cancer. Several studies, including ours, have revealed that GnRH agonists can directly inhibit the growth and proliferation of various human cancer cell lines, including ovarian cancer cell lines, through the GnRHR in a dose- and time-dependent manner ( 8 – 10 , 12 – 14 ). In the present study, we demonstrated that SKOV3, SKOV3-ip and A2780 cells all expressed GnRHR, which may be required for goserelin to act on these three cell lines.…”

“…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 ).…”

“…SKOV3 (1×10 7 /ml) cells were heterotransplanted into 14 nude mice, 6 of which were injected with SKOV3 cells labelled with CM-DiI (Invitrogen). Six CM-DiI-labelled nude mice and the other 8 nude mice were divided randomly into 2 groups respectively: the Goserelin group was subcutaneously injected daily with 100 µg of goserelin in 200 µl of NS ( 14 , 16 , 17 ); the NS group was subcutaneously injected with 200 µl of NS per day. Subcutaneous xenograft tumors in nude mice were monitored by an in vivo imaging system.…”

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

“…Rodents represent the most studied model in reproductive biology. Several in vivo experimental studies have been conducted in both female mice (Table 1) [9,19,[43][44][45][46][47][48][49][50][51][52] and rats (Table 2) [38,39,41,[53][54][55][56][57][58][59][60][61][62] treated with chemotherapy.…”

“…In mice, the majority of the studies showed a positive effect for GnRHa treatment in preventing busulfan-, cisplatin-, docetaxel-, and cyclophosphamide-induced depletion of primordial follicles [44][45][46][47][48][49]51] with a study suggesting that the beneficial protective gonadal effect may depend on the dose of administered chemotherapy [43]. A recent study in mice showed that co-administration of GnRHa during chemotherapy improved oocyte quality and early embryo development after exposure to cyclophosphamide [46].…”