Azidothymidine inhibits NF-kappa B and induces Epstein-Barr virus gene expression in Burkitt lymphoma

作者：Kurokawa M; Ghosh SK; Ramos JC; Mian AM; Toomey NL; Cabral L; Whitby D; Barber GN; Dittmer DP; Harrington WJ^*

来源：Blood, 2005, 106(1): 235-240.

DOI：10.1182/blood-2004-09-3748

The antiviral compound azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early-passage, Epstein-Barr virus-positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's antitumor activity. The nuclei of these cells contain activated nuclear factor-kappa B (NF-kappa B) sub-units p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-kappa B within 1 to 2 hours. This was followed by up-regulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not ganciclovir (GCV) was highly phosphorylated to its monophosphate form (AZT-MID). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-kappa B and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL.

• 出版日期2005-7-1