Antiglioma effects of combined use of a baculovirual vector expressing wild-type p53 and sodium butyrate.

Background: Combination therapy is usually desirable for successful cancer treatment, especially in cancers that are resistant to single forms of therapy.

Methods: To achieve an optimal therapeutic effect against glioblastoma, we tested a strategy that combines baculovirus-mediated transfer of the p53 tumor suppressor gene with the use of sodium butyrate, a histone deacetylase inhibitor. This strategy was designed based on the findings that the transduction efficiency of baculovirus in mammalian cells can be markedly enhanced by the addition of histone deacetylase inhibitors and that these inhibitors are effective in inducing cell cycle arrest, differentiation, or apoptosis in tumor cells.

Results: We observed a synergistic effect of the combination of the two treatments in provoking apoptosis in glioblastoma cells with mutant p53. In a mouse glioma xenograft model, the tumor inhibitory effect of baculovirus-expressed p53 was significantly enhanced by co-administration of sodium butyrate.

Conclusions: These findings suggest a new approach to treat glioblastoma using baculovirus-mediated gene transfer in combination with administration of histone deacetylase inhibitor.