Suppression of growth of H-69 small cell lung carcinoma by antagonists of growth hormone releasing hormone and bombesin is associated with an inhibition of protein kinase C signaling

International Journal of Cancer. Journal International Du Cancer
Celia A KanashiroJ L Varga

Abstract

We investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone and in combination with bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC-3940-II on the growth of H-69 human small cell lung carcinoma (SCLC) xenografted into nude mice. Since the activation of the signaling pathways involving protein kinase C (PKC) and the subsequent steps involving mitogen-activated protein kinase (MAPK) and c-fos and c-jun oncogenes are known to be important mechanisms implicated in cellular growth, we investigated how the blockade of tumoral GHRH receptor splice variants and BN/GRP receptors by these antagonists could interfere with these intracellular signaling pathways. Treatment with GHRH antagonists JV-1-65 or MZ-J-7-110 for 4 weeks significantly (p<0.05) decreased the tumor volume by 22.7+/-3.0% and 36.7 +/- 3.6%, respectively, as compared to controls. A larger decrease in tumor volume of 73.0 +/- 9.5% (p<0.01) was produced by BN/GRP antagonist RC-3940-II and its combination with JV-I-65 caused the greatest tumor reduction of 91.0 +/- 9.8% (p<0.01) vs. controls. H-69 SCLC tumors expressed alpha-, betaII-, delta- and eta-PKC isoforms. Antagonists of GHRH and BN/GRP decreased significantly (p<0.05) the ex...Continue Reading

Citations

Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ferenc G RickLuca Szalontay
Jun 28, 2006·Journal of Neurology, Neurosurgery, and Psychiatry·L SabaterF Graus
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marta ZarandiGabor Halmos
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Florian HohlaCelia A Kanashiro
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Florian HohlaGabor Halmos
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zoltan RekasiPeter Nemeth
Nov 18, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Anton StangelbergerCelia A Kanashiro
Feb 13, 2018·International Journal of Cancer. Journal International Du Cancer·Haibo WangAndrew V Schally
May 3, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sandra Cristea, Julien Sage

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