Goserelin Acetate

Goserelin acetate promoted apoptosis of epithelial ovarian cancer SKOV3, SKOV3-ip and A2780 cells in a concentration-dependent manner as measured by flow cytometry, Hoechst staining and TUNEL staining. The expression of cleaved-caspase-3 and cleaved-PARP was significantly increased after treatment. Human apoptosis gene PCR array revealed that goserelin upregulated members of the tumor necrosis factor and TNF receptor superfamilies, which are downstream targets of forkhead box O1. Goserelin enhanced FOXO1 expression, and siRNA-mediated knockdown of FOXO1 abrogated the induction of apoptosis. Goserelin decreased AKT activity by downregulating p-AKT (Ser473) expression, and FOXO1 upregulation was dependent on the PI3K/AKT pathway. In a subcutaneous xenograft tumor model in female nude mice, daily subcutaneous injection of 100 μg goserelin for 19 days significantly increased the proportion of apoptotic cells in tumor tissues.

Fig. 1 Goserelin upregulates FOXO1 through the PI3K/AKT signaling pathway. (Zhang N.; et al. 2018)

A goserelin acetate loaded poloxamer hydrogel PLGA microsphere with a core-shell di-depot structure was prepared by the double-emulsion solvent evaporation method. The formulation achieved high encapsulation efficiency of 94.16 percent and low initial burst release of less than 2 percent. The microspheres extended the administration interval to 49 days and exhibited 9.36-fold higher relative bioavailability compared to the Zoladex implant. The addition of 1 to 5 percent acetic acid shortened the lag time to 6 days.

Fig. 2 Goserelin Acetate-loaded poloxamer hydrogel PLGA microsphere. (Qi P.; et al. 2019)