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

Karoly Szepeshazi, Slobodan Milovanovic, Karoly Lapis, Kate Groot, Andrew V Schally

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 25μg/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.

Original languageEnglish
Pages (from-to)181-192
Number of pages12
JournalBreast Cancer Research and Treatment
Volume21
Issue number3
DOIs
StatePublished - Oct 1 1992
Externally publishedYes

Fingerprint

Somatostatin
Gonadotropin-Releasing Hormone
Estrogens
Breast Neoplasms
Tumor Burden
Growth
Hormone Antagonists
Epidermal Growth Factor
Neoplasms
LHRH Receptors
IGF Type 1 Receptor
Ovariectomy
Insulin-Like Growth Factor I
Capsules
Therapeutics
Down-Regulation
Binding Sites
Apoptosis
Membranes
vapreotide

Keywords

  • estrogen independent MXT mammary tumor
  • experimental breast cancer
  • LH-RH agonist
  • LH-RH antagonist
  • somatostatin analog RC-160

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Szepeshazi, Karoly; Milovanovic, Slobodan; Lapis, Karoly; Groot, Kate; Schally, Andrew V.

In: Breast Cancer Research and Treatment, Vol. 21, No. 3, 01.10.1992, p. 181-192.

Research output: Contribution to journalArticle

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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 25μg/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.",
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