Abstract 2512: Combining radiation or carboplatin with targeted inhibition of survivin increases treatment induced apoptosis in retinoblastoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 2512
• Main Authors: Luna, Marian, Ferrario, Angela, Rucker, Natalie, Wong, Sam, Gomer, Charles J.
• Format: Journal Article
• Language: English
• Published: 15-04-2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-2512

The overarching goal of this project is to evaluate clinically relevant protocols to improve treatment responses for retinoblastoma (Rb). Procedures to treat Rb vary depending on the size and location of the intraocular lesions and can include carboplatin or radiation therapy. We have preliminary data documenting over expression of survivin, a member of the inhibitor of apoptosis family of proteins, following treatment of Rb cells with either carboplatin or ionizing radiation. The specific aim of the current study is to determine if targeted inhibition of survivin expression using the clinically relevant small molecule imidazolium inhibitor, YM155, can increase selective cytotoxicity in Rb cells. Experimental procedures used Y79 retinoblastoma and RPE normal retinal pigmented epithelial cell lines. Protein expression following either single or combined treatment protocols is examined by Western immunoblot. Levels of apoptosis and cytotoxicity are determined by flow cytometry following Annexin V and propidium iodide staining. We document that both radiation (5 Gy) and carboplatin (5 uM) induce significant over expression of survivin in Y79 cells, but not in RPE cells. Over expression of survivin following radiation or carboplatin is blocked in Y79 cells exposed to YM155 (2 nM). Combining radiation or carboplatin with YM155 resulted in significantly increased levels of apoptosis and cell killing in Y79 cells but not in RPE cells. These results indicate that targeted inhibition of survivin may provide a therapeutic gain when combined with radiation or carboplatin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2512. doi:10.1158/1538-7445.AM2011-2512