Chemosensitization effect of hypoxia inducible factor-1α anti-sense oligodexynucleotide on the model of human laryngeal squamous cell cacinoma in nude mice

Objective To investigate the sensitization effect and the possible pathway of hypoxia inducible factor-1α(HIF-1α) anti-sense oligodexynucleotide in the chemotherapy of human laryngeal squamous cell cacinoma in nude mice.Methods Twenty-eight nude mice were divided into four groups:group A(HIF-1a S-PS-ODN transfection+chemotherapy),group B(HIF-1a AS-PS-ODN transfection+ chemiotherapy),group C(chemiotherapy) and group D(blank for constrol).100 μg DNA was injected into the mice in group A and B(lipofectamine2000∶DNA=1∶1).Mice of all groups were injected with DDP every 48 h.The duration was 16 days.The nude mice were killed 24 h after the last injection.Flow cytometry(FCM) was used for detecting cell apoptosis.The expression of HIF-1α,P53 and VEGF was detected with immunocytochemical method.Results The apoptosis rate of group B(44.75±5.71%) was significantly higher than that of the other 3 groups(P0.01).Proportion of G0/G1 in Group B was significantly lower than those in the other 3 groups(P0.05).Expression of these proteins in Group B was significantly lower than that in the other 3 groups.After transfected by HIF-1α AS-PS-ODN,the expression of HIF-1α,P53,VEGF proteins in Hep-2 cells was restrained.The expression in Hep-2 cells of group B(0.905±0.141,0.773±0.128,0.848±0.068) was significantly lower than that in the other 3 groups(P0.01).Conclusion Treatment strategy in group B may be the most effective in the inhibition of tumors.Expression of P53 protein and VEGF protein may be the major apoptotic pathway.