Effect Of Cf102 On Growth Suppression And Apoptosis In An Orthotopic Model Of Hepatocellular Carcinoma

22113 Background: The A3 adenosine receptor (A3AR), a Gi protein associated cell surface receptor was suggested as a target for cancer treatment. In this study the expression and functionality of the A3AR in Hepatocellular carcinoma (HCC) was examined Methods: RT-PCR, western blot analysis and Immuno-histochemistry were used to evaluate the level of A3AR and cell growth regulatory proteins in tissues and peripheral blood mononuclear cells (PBMCs). A rat orthotopic model of N1S1 HCC tumor cells was used. Results: A3AR was found to be highly expressed in tumor tissues derived from patients and rats with HCC. A3AR over-expression was also found in the PBMCs, reflecting receptor status in the remote organ. The high expression level of the receptor was directly correlated to over expression of NF-ΚB, known as a transcription factor of A3AR. CF102, a synthetic highly selective agonist at the A3AR, induced growth suppression of rat HCC in an orthotropic model when given orally. Analysis of tumor lesions excised from CF102-treated animals demonstrated: a) de-regulation of the NF-κB and the Wnt signal transduction pathways; b) up-regulation of BAD, BAX and Caspase-3 resulting in apoptosis. Conclusions: A3AR is highly expressed in tumors and PBMCs of HCC patients and tumor bearing rats. Oral administration of CF102 induced tumor growth suppression and apoptosis of HCC. These data suggest A3AR as a novel targeted therapy to treat HCC. No significant financial relationships to disclose.