Inhibition of experimental small-cell and non-small-cell lung cancers by novel antagonists of growth hormone-releasing hormone

Haibo Wang, Xianyang Zhang, Irving Vidaurre, Renzhi Cai, Wei Sha, Andrew V Schally

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We investigated the effects of novel antagonists of growth hormone releasing hormone (GHRH)-MIA602 and MIA690-on three human small cell lung cancer (SCLC) lines (H446, DMS53 and H69) and two non-SCLC (NSCLC) lines (HCC827 and H460). In vitro exposure of cancer cells to these GHRH antagonists significantly inhibited cell viability, increased cell apoptosis, decrease cellular levels of cAMP and reduced cell migration. In vivo, the antagonists strongly inhibited tumor growth in xenografted nude mice models. Subcutaneous administration of MIA602 at the dose of 5 μg/day for 4-8 weeks reduced the growth of HCC827, H460 and H446 tumors by 69.9%, 68.3% and 53.4%, respectively, while MIA690 caused a reduction of 76.8%, 58.3% and 54.9%, respectively. Western blot and qRT-PCR analyses demonstrated a downregulation of expression of the pituitary-type GHRH-R and its splice-variant, cyclinD1/2, cyclin-dependent kinase4/6, p21-activated kinase-1, phosphorylation of activator of transcription 3 and cAMP response element binding protein; and an upregulation of expression of E-cadherin, β-catenin and P27kip1 in cancer cells and in xenografted tumor tissues. The study demonstrates the involvement of GHRH antagonists in multiple signaling pathways in lung cancers. Our findings suggest the merit of further investigation with these GHRH antagonists on the management of both SCLC and NSCLC.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Growth Hormone-Releasing Hormone
Non-Small Cell Lung Carcinoma
Hormone Antagonists
Neoplasms
p21-Activated Kinases
Pituitary Hormone-Releasing Hormones
Catenins
Cyclic AMP Response Element-Binding Protein
Cyclins
Small Cell Lung Carcinoma
Cadherins
Growth
Nude Mice
Growth Hormone
Cell Movement
Lung Neoplasms
Cell Survival
Up-Regulation
Down-Regulation
Western Blotting

Keywords

  • GHRH antagonists
  • GHRH receptors
  • NSCLC
  • SCLC
  • Signaling pathways

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Inhibition of experimental small-cell and non-small-cell lung cancers by novel antagonists of growth hormone-releasing hormone. / Wang, Haibo; Zhang, Xianyang; Vidaurre, Irving; Cai, Renzhi; Sha, Wei; Schally, Andrew V.

In: International Journal of Cancer, 01.01.2018.

Research output: Contribution to journalArticle

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