Abstract
The effects of antagonists of bombesin/gastrin-releasing peptide (GRP) on the growth of human malignant glioblastoma cell line U-87MG xenografted into nude mice were evaluated. Nude mice bearing s.c. implanted U-87MG tumors were treated with bombesin/GRP antagonists RC-3095 and RC-3940-II. RC-3095 and RC-3940-II administered s.c. at a dose of 20 μg/day for 4 weeks decreased the volume of U-87MG xenografts by 60 and 74%, respectively, compared with controls. RT – PCR analysis showed that U-87MG xenografts expressed mRNA for bombesin receptor subtype (BRS)-1 (GRP receptor) and BRS-2 (neuromedin-B receptor), but the mRNA for GRP ligand was not detected in U-87MG cells suggesting that GRP may stimulate the growth of U-87MG glioblastomas by a paracrine mechanism. The levels of mRNA for c-fos oncogene were decreased by 30 – 40% in U-87MG tumors treated with RC-3095 or RC-3940-II. In U-373MG glioblastoma cells, which also express BRS-1, and U-87MG cells, cultured in vitro, GRP(14 – 27) induced the expression of c-fos mRNA, and some c-jun mRNA, in a time-dependent manner with the maximal effect occurring 2 h after the stimulation and a return to basal levels after 8 h. Antagonist RC-3940-II inhibited the stimulation of c-fos by GRP(14 – 27). Our results indicate that antagonists of bombesin/GRP inhibit the growth of U-87MG glioblastomas by a mechanism that may involve the downregulation of c-fos oncogene.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Draoui M, Chung P, Park M, Birrer M, Jakowlew S and Moody TW. . 1995 Peptides 16: 289–292.
Draoui M, Moody TW, Fahti Z and Battey J. . 1993 Cell Growth Differ. 4: 723–729.
Halazonetis TD, Georgopoulos K, Greenberg ME and Leder P. . 1988 Cell 55: 917–924.
Halmos G and Schally AV. . 1997 Proc. Natl. Acad. Sci. USA 94: 956–960.
Hochberg F and Pruitt A. . 1987 In: Harrison's Principles of Internal Medicine, 11th ed. Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB and Fauci S (eds.). McGraw-Hill: New York pp. 1968–1980.
Koppan M, Halmos G, Arencibia JM, Lamharzi N and Schally AV. . 1998 Cancer 83: 1335–1343.
Liebow C, Crean DH, Lee MT, Kamer AR, Mang TS and Schally AV. . 1994 Proc. Natl. Acad. Sci. USA 91: 3804–3808.
Mahmoud S, Staley J, Taylor J, Bogden A, Moreau J-P, Coy D, Avis I, Cuttitta F, Mulshine JL, Moody TW. . 1991 Cancer Res. 51: 1798–1802.
Moody TW and Pert CB. . 1979 Biochem. Biophys. Res. Commun. 90: 7–14.
Moody TW, Mahmoud S, Staley J, Naldini L, Cirillo D, South V, Felder S and Kris R. . 1989 J. Mol. Neurosci. 1: 235–242.
Moody TW, Murphy A, Mahmoud S and Fiskum G. . 1987 Biochem. Biophys. Res. Commun. 147: 189–195.
Moody TW, Pert CB, Gazdar AF, Carney DN and Minna JD. . 1981 Science 214: 1246–1248.
O'Shea EK, Rutkowski R, Stafford WF 3d and Kim PS. . 1989 Science 245: 646–648.
Olson JJ, Beck DW, MacIndoe JW and Min-Loh P. . 1988 Cancer 61: 952–957.
Paoletti P, Butti G, Zibera C, Scerrati C, Gibelli N, Roselli R, Magrassi L, Sica G, Rossi G and Della Cuna GR. . 1990 J. Neurosurg. 73: 736–742.
Pinski J, Halmos G, Shirahige Y, Wittliff JL and Schally AV. . 1993 J. Clin. Endocrinol. Metab. 77: 1388–1392.
Pinski J, Halmos G, Yano T, Szepeshazi K, Qin Y, Ertl T and Schally AV. . 1994b Int. J. Cancer 57: 574–580.
Pinski J, Reile H, Halmos G, Groot K and Schally AV. . 1994c Cancer Res. 54: 169–174.
Pinski J, Schally AV, Halmos G, Szepeshazi K, Groot K, O'Byrne K and Cai R-Z. . (1994a).Br. J. Cancer 70: 886–892.
Pinski J, Schally AV, Halmos G, Szepeshazi K and Groot K. . 1994d Cancer Res. 54: 5895–5901.
Poisson M, Pertuiset BF, Hauw J-J, Philippon J, Buge A, Moguilewsky M and Philibert D. . 1983 J. Neurooncol. 1: 179–189.
Qin Y, Ertl T, Cai R-Z, Halmos G and Schally AV. . 1994a Cancer Res. 54: 1035–1041.
Qin Y, Halmos G, Cai R-Z, Szoke B, Ertl T and Schally AV. . 1994b J. Cancer Res. Clin. Oncol. 120: 519–528.
Radulovic S, Cai R-Z, Serfozo P, Groot K, Redding TW, Pinski J and Schally AV. . 1991 Int. J. Pept. Protein Res. 38: 593–600.
Reile H, Cai R-Z, Armatis P and Schally AV. . 1995 Int. J. Oncol. 7: 749–754.
Schally AV and Comaru-Schally AM. . 1997 In: Cancer Medicine, 4th Ed. Holland JF, Frei III E, Bast Jr RC., Kufe DE, Morton DL and Weichselbaum RR . (eds). Williams and Wilkins Publishers: Baltimore pp. 1067–1086.
Sharif TR, Luo W and Sharif M. . (1997) Mol. Cell Endocrinol. 130: 119–130
Schoenberg BS. . 1983 In: Oncology of the Nervous System. Walker MD. (ed.) Nijhoff: Boston, USA pp. 1–30.
Siegfried JM, Han Y-H, DeMichele MAA, Hunt JD, Gaither AL and Cuttitta F. . 1994 J. Biol. Chem. 269: 8596–8603.
Spindel ER, Giladi E, Segerson TP and Nagalla S. . 1993 Rec. Prog. Horm. Res. 48: 365–391.
Staley J, Coy DH, Jensen RT and Moody TW. . 1993 J. Mol. Neurosci. 4: 29–50.
Szepeshazi K, Schally AV, Cai R-Z, Radulovic, S, Milovanovic S and Szoke B. . 1991 Cancer Res. 51: 5980–5986.
Szepeshazi K, Schally AV, Halmos G, Groot K and Radulovic S. . 1992 J. Natl. Cancer Inst. 84: 1915–1921.
Wang QJ, Knezetic JA, Schally AV, Pour PM and Adrian TE. . 1996 Int. J. Cancer 68: 1–7.
Yano T, Pinski J, Groot K and Schally AV. . 1992 Cancer Res. 52: 4545–4547.
Acknowledgements
We thank Harold Valerio for excellent technical assistance. We are grateful to ASTA Medica (Frankfurt/Main, Germany) for D-22213 (RC-3095) and D-24197 (RC-3940-II). Some work described in this paper was supported by a grant of ASTA Medica to Tulane University (Frankfurt on Main, Germany) and the Medical Research Service of the Veterans Affairs Department (to AV Schally).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kiaris, H., Schally, A., Sun, B. et al. Inhibition of growth of human malignant glioblastoma in nude mice by antagonists of bombesin/gastrin-releasing peptide. Oncogene 18, 7168–7173 (1999). https://doi.org/10.1038/sj.onc.1203213
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203213
Keywords
This article is cited by
-
Gastrin-Releasing Peptide Receptor Knockdown Induces Senescence in Glioblastoma Cells
Molecular Neurobiology (2017)
-
Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways in small cell lung carcinoma
Oncogene (2015)
-
Anti-EGFR therapy combined with neuromedin B receptor blockade induces the death of DAOY medulloblastoma cells
Child's Nervous System (2013)
-
N(4)-Tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action
BioMetals (2013)
-
BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells
Journal of Molecular Neuroscience (2010)