Study on the effects of gonadotropin-releasing hormone analogues in the inhibition of ovarian cancer transplanted tumors and in the protection of ovarian function after chemotherapy on nude mice

Abstract

To investigate the influence of gonadotropin-releasing hormone (GnRH) analogues on ovarian cancer and ovarian function in vivo. ES-2 cells were cultured and xenotransplanted into 36 nude mice, which were divided into 6 groups: normal saline (NS) group: NS 0.1 ml/day subcutaneous injection, and then NS 0.2 ml/week peritoneal injection; cisplatin (DDP) group: NS 0.1 ml/day subcutaneous injection, and then DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; goserelin group: 100 µg goserelin (diluted to 0.1 ml) per day subcutaneous injection, and then NS 0.2 ml/week peritoneal injection; goserelin + DDP group: 100 µg goserelin (diluted to 0.1 ml) per day subcutaneous injection, and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; cetrorelix group:100 µg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and NS 0.2 ml/week peritoneal injection; cetrorelix + DDP group: 100 µg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection. All the peritoneal injection started from subcutaneous injection one week later. To compare the weight of nude mice, the volumes of transplanted tumors, the expression of Ki-67 antigen in transplanted tumors, the estrus, the ratio of atretic follicles, the ratio of primary and preantral follicles, the levels of serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradio (E(2)) and progesterone (P) in each group. There were no significant difference in the weight of nude mice among 6 groups (P > 0.05), which on day 29 in NS group was (19.8 ± 2.2) g, DDP group (20.5 ± 1.4) g, gosereline group (19.6 ± 0.9) g, goserelin + DDP group (19.7 ± 1.6) g, cetrorelix group (20.7 ± 2.2) g, and cetrorelix + DDP group (19.0 ± 1.7) g. The tumor volumes of different groups on the 12(th) day: NS group (241 ± 179) mm(3), DDP group (78 ± 20) mm(3), gosereline group (78 ± 55) mm(3), goserelin + DDP group (64 ± 48) mm(3), cetrorelix group (78 ± 64) mm(3), or cetrorelix + DDP group (70 ± 19) mm(3), in which there were significant difference between NS group and the other groups (P < 0.05); and the same result was obtained on day 15, 19, 22, 26 and 29 (P < 0.05). The expression of Ki-67 in NS group was (33 ± 10)%, in which it was higher than those in DDP group 3.5%, goserelin group 8.8%, goserelin + DDP group 1.5%, cetrorelix group (23 ± 11)%, or cetrorelix + DDP group (8 ± 6)% (P < 0.05). The ratio of primary and preantral follicles in goserelin group was (71.5 ± 8.1)%, in goserelin + DDP group was (62.4 ± 4.1)%, in cetrorelix group was (71.2 ± 7.4)%, and in cetrorelix + DDP group was (63.8 ± 3.1)%, in which they were much higher than that in DDP group (47.0 ± 4.8)% (P < 0.05). The level of AMH in goserelin group was (98 ± 27) ng/ml, which was much higher than that in NS group (66.2 ± 17.4) ng/ml (P < 0.05), while there were no difference in the levels of FSH, E(2) or P among different groups (P > 0.05). GnRH analogues could inhibit the growth of transplanted tumors in nude mice, meanwhile increase the secretion of AMH, decrease the frequencies and prolong the lasting time of estrus, decrease the ratio of atretic follicles, raise the ratio of primary and preantral follicles, which may be protect the ovarian function of nude mice.