Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer

Jacek Pinski, Herta Reile, Gabor Halmos, Kate Groot, Andrew V Schally

Research output: Contribution to journalArticle

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Abstract

The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 μg/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 μg/ day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 μg/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalCancer Research
Volume54
Issue number1
StatePublished - Jan 1 1994
Externally publishedYes

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Gastrin-Releasing Peptide
Bombesin
Somatostatin
Androgens
Prostatic Neoplasms
Growth
Tumor Burden
Bombesin Receptors
Neoplasms
Binding Sites
vapreotide
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Somatostatin-Secreting Cells
Castration
Insulin-Like Growth Factor I
Epidermal Growth Factor
Growth Hormone
Capsules
Prostate
Adenocarcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer. / Pinski, Jacek; Reile, Herta; Halmos, Gabor; Groot, Kate; Schally, Andrew V.

In: Cancer Research, Vol. 54, No. 1, 01.01.1994, p. 169-174.

Research output: Contribution to journalArticle

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