Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer

  • Authors:
    • Celia A. Kanashiro
    • Andrew V. Schally
    • Marta Zarandi
    • Brian D. Hammann
    • Jozsef L. Varga
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/ijo.30.4.1019
  • Pages: 1019-1028
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Abstract

New therapeutic strategies are necessary to improve the treatment of lung cancer. We investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonist, RC-3940-II, and growth hormone-releasing hormone (GHRH) antagonists, MZ-J-7-114 and MZ-J-7-118, on the expression of epidermal growth factor receptor (EGFR)/HER (-2, -3, and -4) family, angiogenic factors, VEGF-A and VEGF receptors (VEGF-R1 and VEGF-R2), and the apoptotic molecules Bax and Bcl-2, in H-460 and A-549 non-small cell lung carcinomas (NSCLC). Nude mice bearing xenografts of H-460 and A-549 NSCLC were treated daily with these peptide analogues for 4 weeks. The treatment resulted in growth inhibition of H-460 by 22-77% and A-549 NSCLCs by 64-84%. The inhibition of tumor growth was associated with a down-regulation of members of EGFR/HER family. A significant reduction of the levels of expression of EGFR/HER family on both tumors varied from 29-96%: the greatest inhibition being induced by RC-3940-II. Similarly, a significant decrease in the levels of VEGF-A in tumors by 19-60% and VEGF receptors (VEGF-R1, 24-74% and VEGF-R2, 25-50%) was detected after therapy. An up-regulation of Bax by 21-63% and a down-regulation of Bcl-2 by 23-39% was observed only for H-460 NSCLC. Our study demonstrates that human H-460 and A-549 NSCLC, express receptors for GHRH and bombesin/GRP, and respond to the respective antagonists. The antagonists of bombesin/GRP and GHRH could provide a new strategy for treatment of NSCLC through down-regulation of EGFR/HER family and an interference with the angiogenic and apoptotic pathways.

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April 2007
Volume 30 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Kanashiro, C.A., Schally, A.V., Zarandi, M., Hammann, B.D., & Varga, J.L. (2007). Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer. International Journal of Oncology, 30, 1019-1028. https://doi.org/10.3892/ijo.30.4.1019
MLA
Kanashiro, C. A., Schally, A. V., Zarandi, M., Hammann, B. D., Varga, J. L."Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer". International Journal of Oncology 30.4 (2007): 1019-1028.
Chicago
Kanashiro, C. A., Schally, A. V., Zarandi, M., Hammann, B. D., Varga, J. L."Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer". International Journal of Oncology 30, no. 4 (2007): 1019-1028. https://doi.org/10.3892/ijo.30.4.1019