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Int J Cancer. 2009 Feb 1;124(3):622-9. doi: 10.1002/ijc.23993.

An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth and infiltration of EBV-positive lymphoblastoid B cells.

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1
Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Abstract

Epstein-Barr Virus (EBV)-associated immunoblastic lymphoma occurs in immunocompromised patients such as those with AIDS or transplant recipients after primary EBV infection or reactivation of a preexisting latent EBV infection. In the present study, we evaluated the effect of ritonavir, an HIV protease inhibitor, on EBV-positive lymphoblastoid B cells in vitro and in mice model. We found that it induced cell-cycle arrest at G1-phase and apoptosis through down-regulation of cell-cycle gene cyclin D2 and antiapoptotic gene survivin. Furthermore, ritonavir suppressed transcriptional activation of NF-kappaB in these cells. Ritonavir efficiently prevented growth and infiltration of lymphoma cells in various organs of NOD/SCID/gammacnull mice at the same dose used for treatment of patients with AIDS. Our results indicate that ritonavir targets NF-kappaB activated in tumor cells and shows anti-tumor effects. These data also suggest that this compound may have promise for treatment or prevention of EBV-associated lymphoproliferative diseases that occur in immunocompromised patients.

PMID:
18973272
DOI:
10.1002/ijc.23993
[Indexed for MEDLINE]
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