Direct effect of a gonadotropin‐releasing hormone agonist on the growth of canine mammary tumour cells

Abstract

Gonadotropin-releasing hormone (GnRH) agonist exert "in vivo" an inhibitory action on the growth of hormone-dependent canine mammary tumours (Lombardi et al. [1999] J. Vet. Pharmacol Ther. 22(1):56-61). The present experiments have been performed "in vitro" in order to investigate the mechanisms involved in this direct antiproliferative action of GnRH agonists. In particular, the aim was to study whether these compounds might exert their antiproliferative effect by interfering with the stimulatory action of epidermal growth factor (EGF). To this purpose, the effects of GnRH agonist, Goserelin (GnRH-A), on the mitogenic action of EGF, on EGF-activated intracellular signaling mechanisms (intracellular calcium and nitric oxide production) as well as on ATP induced cell proliferation and signalling, and on the binding of EGF receptors have been evaluated in primary culture of canine mammary tumour cells. The results of these "in vitro" studies show that GnRH-A counteracts the mitogenic action of EGF and ATP, decreases the EGF/ATP-induced calcium signalling and reduces EGF binding, probably by means of NO-induced [Ca2+]i downregulation. These data suggest that GnRH agonists may inhibit the proliferation of the tumour cells by interfering with the stimulatory action of EGF.

Hydrocortisone has a protective effect on CyclosporinA‐induced cardiotoxicity

“…Intracellular Ca 2+ concentrations [Ca 2+ ] i were measured by using the radiometric fluorescent indicator dye FURA‐2/AM, the membrane‐permeant form of FURA‐2 as previously described and opportunely modified (Pagnini et al, 2002). Rat cardiomyocytes were resuspended in Krebs Ringer (KRH) medium (1 × 10 7 cells/ml) with 3.0 μM Ca 2+ ‐sensitive dye FURA‐2/AM for 120 min at 30°C.…”

Clinical Use of GnRH Agonists in Canine and Feline Species

“…Lombardini et al (1999) showed that goserelin 60 mg ⁄ kg given every 3 weeks reduced the size of mammary tumours after 3 months in nine study bitches. The same team also investigated the effects of goserelin on bitch mammary cancer cells cultured in vitro (Pagnini et al 2002) and showed that the agonist was also able to inhibit the mitogenic effects of a growth factor, EGF (Epithelial Growth Factor) which promotes the growth of mammary tumours. This effect on the tumours may be related to a direct effect by the agonist on the tumour cells, not a spaying effect.…”

“…Besides, such effects are highly suspected in the dog, particularly on urinary function (Reichler et al. 2006a) or mammary tumours (Pagnini et al. 2002).…”

“…GnRH agonists may therefore have a direct action on these organs, even if this has not yet been clearly elucidated. Besides, such effects are highly suspected in the dog, particularly on urinary function (Reichler et al 2006a) or mammary tumours (Pagnini et al 2002).…”

Clinical and Endocrine Short-Term Effects of GnRH Analogue Deslorelin in Prepubertal Bitches: Does A “Flare-up” Occur?

“…Long-acting GnRH agonists can be used for indications such as preventing puberty in both sexes; controlling of estrus cycle and treating post-spaying urinary incontinence [3][4][5][6] and controlling the risk of recurrence of mammary neoplasia, prevention of mammary tumour metastatic disease and the termination of pregnancy in bitches [7][8][9] .…”