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WAI KIT CHU, Fuk Loi Benjamin Li, Ka Sin Law, SUNON CHAN, Herman S Cheung, Andrew V Schally, Chi Pui Calvin Pang; Growth hormone-releasing hormone (GHRH) antagonist induces apoptosis in retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3661.
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© ARVO (1962-2015); The Authors (2016-present)
Growth hormone-releasing hormone (GHRH) and its receptor (GHRHR) have been shown to correlate with proliferation and survival of several reported malignancies. In this study we investigated an extra-pituitary role of GHRHR in retinoblastoma (RB), with further exploration of novel GHRHR antagonists and agonist in inducing apoptosis in retinoblastoma cells.
Expression pattern of GHRHR in Y79 retinoblastoma was thoroughly characterized in terms of immunoblot determination, subcellular localization as well as populational distribution. GHRHR expressions in normal retinal cell lines of ARPE19 retinal pigmented epithelium and SVG neuroglia were compared with Y79. Effects of GHRH antagonist MIA602, MIA690 and agonist MR409 on Y79 were evaluated with respect to apoptosis induction.
GHRHR were shown qualitatively and quantitatively overexpressing in Y79 retinoblastoma in comparison to ARPE19 and SVG. GHRHR-expressing cells contributed to the whole population of Y79, with subcellular localization featured as cytoplasmic and/or cell surface expression. GHRHR antagonists MIA-602 and MIA-690 demonstrated pro-apoptotic effects, while GHRHR agonist MR-409 did not show any effect in inducing apoptosis. MIA-602 regulated gene signaling in relation to proliferation and apoptosis such as upregulating gene expression of Caspase 3 and downregulating gene expression of ERK1 and ERK2.
Differential GHRHR overexpression of retinoblastoma in retina has implied its susceptibility as a selective molecular target for anti-cancer therapy. This study has further indicated GHRHR blockage can be a potential strategy against retinoblastoma via induction of apoptosis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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