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.
Institute of Bioengineering and Nanotechnology, Singapore.
Haiyan
H
Guo
Yukti
Y
Choudhury
Jing
J
Yang
Can
C
Chen
Felix Chang
FC
Tay
Tit Meng
TM
Lim
Shu
S
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D016367:Baculoviridae / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods*; D005260:Female; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005910:Glioma / Q000628:therapy; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D016159:Tumor Suppressor Protein p53