Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75

Tetsu Yano, Jacek Pinski, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Andrew V Schally

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Abstract

Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)- releasing hormone (LH-RH) antagonist SB-75 {Cetrorelix; [Ac-D-Nal(2)1, D- Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N- acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4Cl) = 4-chloro-D-phenylalanine, D- Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline} or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 μg/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 μg/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma.

Original languageEnglish
Pages (from-to)7090-7094
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number15
DOIs
StatePublished - Jul 19 1994
Externally publishedYes

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Hormone Antagonists
Heterografts
Nude Mice
Gonadotropin-Releasing Hormone
Luteinizing Hormone
Growth
Tumor Burden
Ovarian Neoplasms
Therapeutics
Neoplasms
Citrulline
Ovarian epithelial cancer
cetrorelix
Phenylalanine
Insulin-Like Growth Factor I
Capsules
Cell Membrane
Carcinoma
Weights and Measures
Cell Line

Keywords

  • analogs of luteinizing hormone-releasing hormone
  • gynecologic cancers
  • ovarian carcinoma
  • selective medical hypophysectomy

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75. / Yano, Tetsu; Pinski, Jacek; Halmos, Gabor; Szepeshazi, Karoly; Groot, Kate; Schally, Andrew V.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 15, 19.07.1994, p. 7090-7094.

Research output: Contribution to journalArticle

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abstract = "Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)- releasing hormone (LH-RH) antagonist SB-75 {Cetrorelix; [Ac-D-Nal(2)1, D- Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N- acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4Cl) = 4-chloro-D-phenylalanine, D- Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline} or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 μg/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 μg/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma.",
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