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Sofia Theodoropoulou, Maki Kayama, Yuki Morizane, Yusuke Murakami, Eva Nong, Evangelos Gragoudas, Joan W. Miller, Demetrios G. Vavvas; AICAR, An Exercise Mimetic, Inhibits The Growth Of Retinoblastoma In Vivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2106.
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5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. The aim of this study is to evaluate the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo.
The in vivo effects of AICAR on subcutaneously transplanted Y79 cells (human retinoblastoma) in BALB/c nude mice were studied, examining tumor size and performing histopathological evaluations of excised tumors including hematoxylin and eosin and immunohistochemical staining (Ki67, TUNEL assay, CD31, CD11b).
AICAR markedly (more than 50%) reduced the growth of Y79 cell tumors in mice without producing systemic toxicity. Pathological findings of the tumor mass isolated from mice revealed that the tumor of Y79 cells treated with AICAR had a decreased mitotic index, decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed tumor angiogenesis and macrophage infiltration.
Our results indicate that treatment with AICAR inhibited the growth of retinoblastoma tumor in vivo. AICAR is a promising novel non-chemotherapeutic drug with low toxicity that may be effective in treating Retinoblastoma patients.
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