Background: The aim of this study is to assess the therapeutic effect of the PUMA gene mediated by radiation-inducible promoter in the treatment of tongue squamous cell carcinoma.
Methods: Recombinant pcDNA3.1(+)/E-PUMA was constructed, in which the PUMA gene was mediated by a synthetic radiation-inducible promoter. The recombined plasmids were transfected into Tca8113 cells and xenografts of human tongue squamous carcinoma in naked mice. After 24 h, the tumors were treated with 3 Gy of radiation to upregulate PUMA gene expression. PUMA mRNA was detected by RT-PCR. Proliferating cell nuclear antigen and apoptosis were detected by immunohistochemical method and in situ end-labeling (ISEL), respectively. The data were analyzed using the SPSS 11.0 software package for chi-square test.
Results: Compared with the control group, the comparative survival rate of Tca8113 cells in the PUMA/IR group was markedly decreased and the xenografts were significantly suppressed. Upregulation of PUMA gene expression was observed in the Tca8113 cells and in the xenografts after irradiation. The apoptosis indices of the Tca8113 cells and xenografts with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indices of the Tca8113 cells and xenografts with irradiation were markedly lower than those without irradiation.
Conclusions: Radiation-inducible promoters can serve as molecular switches to improve the expression of PUMA gene in tongue squamous cell carcinoma both in vivo and in vitro. Low-dose induction radiation can significantly improve the therapeutic efficiency. Validating this strategy in the targeted treatment of tongue squamous cell carcinoma is possible.
Conflict of interest: This study was supported by the National Natural Sciences Foundation of China (Grant no. 30973340), the Guangdong Sciences and Technology Project (Grant nos. 2008B030301113 and 2007B031505007), and the Guangdong Natural Sciences Foundation (Grant no. 9151008901000187).