We have earlier shown that treatment with gonadotropin releasing hormone antagonist blocked adrenocortical tumour progression through gonadotropin suppression in inhibin α/SV40 T-antigen (inhα/Tag) transgenic (TG) mice. Hereby, we investigated the molecular mechanisms underlying the GnRH antagonist (Cetrorelix acetate; GnRH-a) treatment induced potential antitumor effects on gonadal somatic cell and adrenocortical tumors in vivo and in vitro. In vitro treatment with 10 μM GnRH-a significantly decreased cell viability and proliferation of murine KK1 (granulosa cell), BLT1 (Leydig cell), Cα1 (adrenocortical), all three lines originating from inhα/Tag mice tumors, compared to respective non-treated controls. Flow cytometric analysis revealed a cell cycle arrest at G1 phase in all treated cell lines. We treated in vivo 6-mo-old inhα/Tag mice bearing gonadal or 6.5-mo-old mice bearing adrenal tumors for 21 days, with either 3 mg/kg b.w./48 h i.p. of GnRH-a or vehicle. Treatments revealed a significant reduction of tumor burden in all types of tumours with GnRH-a treatment vs vehicle treated group. Our results suggest that GnRH-a treatment, besides blocking the release of gonadotropins, may also directly induce tumour cell death.
Disclosure: Singrid Juselius Foundation
Academy of Finland