Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP

Y. Qin, T. Ertl, R. Z. Cai, J. Horváth, K. Croot, A. V. Schally

Research output: Contribution to journalArticle

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Abstract

We investigated the effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of SW-1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW-1990 tumors received s.c. injections of RC-3095 and RC-3940-II or the vehicle (control) for 28 days. Chronic administration of RC-3940-II Inhibited the growth of SW-1990 tumors, as shown by a reduction in tumor volume during the treatment and a significant increase in tumor doubling time. RC-3940-II decreased final tumor volume by 57.7% and tumor growth rate by 65%. Final tumor weights in mice treated with RC-3940-II were 75% lower than in controls. Treatment with RC-3095 induced smaller, and not significant, decreases in tumor volume and weight. In cell cultures, both RC-3095 and RC-3940-II effectively inhibited the proliferation of SW-1990 cells, inducing a dose- and time-dependent decrease in the number of cells. RC-3940-II again suppressed in vitro growth of SW-1990 cells more effectively than RC-3095. After 72 hr of culture, RC-3940-II and RC-3095 at 1 μM concentrations decreased cell numbers by 45.7% and 27.7%, respectively. The estimated EC50 value for RC-3940-II was 1 nM. When SW-1990 cells were cultured in the presence of 1 nM and 10 nM RC-3095 for 72 hr, cAMP levels in the incubation medium were decreased to 77.3% and 26.9% of the control value. Our results indicate that bombesin/GRP antagonist RC-3940-II can inhibit the proliferation of SW-1990 human pancreatic adenocarcinoma cells in vivo and in vitro. Our findings also suggest that this effect may involve the intracellular cAMP pathway.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalInternational Journal of Cancer
Volume63
Issue number2
DOIs
Publication statusPublished - 1995

Fingerprint

Gastrin-Releasing Peptide
Bombesin
Cyclic AMP
Adenocarcinoma
Growth
Tumor Burden
Nude Mice
Neoplasms
Cell Count
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Cultured Cells
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP. / Qin, Y.; Ertl, T.; Cai, R. Z.; Horváth, J.; Croot, K.; Schally, A. V.

In: International Journal of Cancer, Vol. 63, No. 2, 1995, p. 257-262.

Research output: Contribution to journalArticle

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abstract = "We investigated the effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of SW-1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW-1990 tumors received s.c. injections of RC-3095 and RC-3940-II or the vehicle (control) for 28 days. Chronic administration of RC-3940-II Inhibited the growth of SW-1990 tumors, as shown by a reduction in tumor volume during the treatment and a significant increase in tumor doubling time. RC-3940-II decreased final tumor volume by 57.7{\%} and tumor growth rate by 65{\%}. Final tumor weights in mice treated with RC-3940-II were 75{\%} lower than in controls. Treatment with RC-3095 induced smaller, and not significant, decreases in tumor volume and weight. In cell cultures, both RC-3095 and RC-3940-II effectively inhibited the proliferation of SW-1990 cells, inducing a dose- and time-dependent decrease in the number of cells. RC-3940-II again suppressed in vitro growth of SW-1990 cells more effectively than RC-3095. After 72 hr of culture, RC-3940-II and RC-3095 at 1 μM concentrations decreased cell numbers by 45.7{\%} and 27.7{\%}, respectively. The estimated EC50 value for RC-3940-II was 1 nM. When SW-1990 cells were cultured in the presence of 1 nM and 10 nM RC-3095 for 72 hr, cAMP levels in the incubation medium were decreased to 77.3{\%} and 26.9{\%} of the control value. Our results indicate that bombesin/GRP antagonist RC-3940-II can inhibit the proliferation of SW-1990 human pancreatic adenocarcinoma cells in vivo and in vitro. Our findings also suggest that this effect may involve the intracellular cAMP pathway.",
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