Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH, an analog of somatostatin, or a combination

Abstract

Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25 micrograms/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40-53% inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.

Management of Breast Cancer: Is There a Role for Somatostatin and Its Analogs?

“…The molecular basis for the attenuation of this antiproliferative effect has not been elucidated. However, consistent with this effect is the observation that antitumor activity of octreotide in the MXT breast tumor model was enhanced by the coadministration of an LHRH analog, which lowers estradiol levels [79]. Moreover, the activity of octreotide was maximized in the absence of estrogens [78].…”

Targeted cytotoxic analogue of bombesin/ gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice

“…Tumour samples were processed as described (Szepeshazi et al, 1992). The extent of necrosis was evaluated with the pointcounting method on tumour slides stained with haematoxylin and eosin (H&E).…”

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

“…Complementary experiments were carried out in in vivo and in vitro models. In a mouse model treated with GnRH agonist, expression of both growth factor receptors was decreased (127). In 4OH-tamoxifenresistant MCF-7 and T47D-TR cells, some GnRH analogs were able to abolish cell proliferation, blocking EGF-receptor autophosphorylation, ERK1/2 activation (128), and reducing EGF-induced c-fos protein expression (129) (Fig.…”