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Inhibition of growth of human malignant glioblastoma in nude mice by antagonists of bombesin/gastrin-releasing peptide

Oncogene volume 18, pages 7168–7173 (1999)Cite this article

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.

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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).

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  1. Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, 70112-1262, Louisiana, LA, USA

    H Kiaris, A V Schally, B Sun, P Armatis & K Groot

  2. Department of Medicine, Section of Experimental Medicine, Tulane University School of Medicine, New Orleans, 70112, Louisiana, LA, USA

    H Kiaris, A V Schally & B Sun

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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

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