[Gene therapy for tongue carcinoma mediated by oral administration of attenuated Salmonella harboring tip30 and IFN-γ genes in nude mouse model].

PURPOSE: To observe the effect of gene therapy mediated by oral administration of attenuated Salmonella carrying tip30 and IFN-γ genes in human tongue carcinoma nude mouse model.

METHODS

25 four-week-old BALB/C male nude mice were divided randomly into 5 groups based on the differently harboring genes in the recombinant attenuated Salmonella typhimuriums SL7207, which included blank group (PBS), control group (SL7207), IFN treatments group (SL7207-pCI-IFN), tip30 treatment group (SL7207-pCI-tip30) and the combination of IFN and tip30 treatment group (SL7207-pCI-tip30/IFN). On 10d after submandibular subcutaneous injection of Tca8113 cells into the mice, the recombinant attenuated Salmonella typhimuriums were orally administrated 3 times at 1 week interval. The treatment effect indicators included the growth curve, the tumor inhabitation rate, the survival rate, the apoptosis typical DNA ladder and the protein expressions of tip30 and IFN-γ in tumor cells. Statistical analysis was performed with SPSS15.0 software package.

RESULTS

The growth curve, the tumor inhabitation rate and the survival rate indicated that the tumor in the PBS group constantly grew up and induced the animal death in earlier time, while the SL7207 treatment had a slight inhibiting effect compared with PBS group. However, the SL7207-pCI-IFN group and the SL7207-pCI-tip30 had a moderate inhibiting effect compared with the SL7207 group, while the combination of IFN and tip30 had the strongest inhibiting effect. The protein expressions of tip30 and IFN-γ were detected in tumor cells while the typical DNA ladders of apoptosis were observed only in the tip30 gene transfer groups (SL7207-pCI-tip30 and SL7207-pCI-tip30/IFN).

CONCLUSIONS

The recombinant attenuated Salmonella typhimurium possesses a capacity of gene transfer in vivo through oral administration. The combination of the harboring tip30 and IFN-γ genes have synergistic inhibiting tumor effect for tongue carcinoma.