Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression

B. Szende, G. Srkalovic, A. V. Schally, K. Lapis, K. Groot

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 μg/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 μg/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect of pancreatic cancers than the regimens previously used (5-25 μg/day). RC-160 D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85% as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.

Original languageEnglish
Pages (from-to)2279-2290
Number of pages12
JournalCancer
Volume65
Issue number10
DOIs
Publication statusPublished - 1990

Fingerprint

Triptorelin Pamoate
Somatostatin
Pancreatic Neoplasms
Gonadotropin-Releasing Hormone
Cricetinae
Neoplasms
IGF Type 1 Receptor
nitrosobis(2-oxopropyl)amine
Insulin-Like Growth Factor I
Capsules
Peptide Receptors
Mesocricetus
vapreotide
Tumor Burden
Cell Death
Down-Regulation
Electrons
Apoptosis
Light
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression. / Szende, B.; Srkalovic, G.; Schally, A. V.; Lapis, K.; Groot, K.

In: Cancer, Vol. 65, No. 10, 1990, p. 2279-2290.

Research output: Contribution to journalArticle

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abstract = "Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 μg/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 μg/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect of pancreatic cancers than the regimens previously used (5-25 μg/day). RC-160 D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85{\%} as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.",
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