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The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC or Cidofovir) on proteomic profiles of Epstein-Barr virus (EBV)-associated lymphoma grown in SCID mouse was evaluated. Intratumoral injection of Cidofovir arrested tumor growth within 10 days and by 21 days tumor regressed to 25 ± 8% of the original size. We isolated proteins from control and drug-treated tumors and did two-dimensional gel electrophoresis to determine protein expression patterns. Fifteen proteins showed significantly differential expression level between control and Cidofovir-treated samples. These proteins were characterized and identified by LC-MS/MS and confirmed by Western blotting. Among these differentially expressed proteins we found that prohibitin, a tumor suppressor protein, was over-expressed in tumors that had been treated with Cidofovir. The expression level of prohibitin correlated with the tumor regression. We established differential proteomic profiles that characterize and distinguish the Cidofovir-treated tumors from the control tumors. The proteins and proteomic profiles enhance understanding of the pathogenesis of EBV and have implications for diagnosis, prognosis, and treatment.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007