Influences Of HIF-1α Antisense Oligodeoxynucleotide On Expressions Of HIF-1α,GLUT-1,MMP-2 In Human Lung Carcinoma Xenografts In Nude Mice

Objective: To explore the inhibitory effects of HIF-1αantisense oligodeoxynucleotide on the growth of human lung carcinoma xenografts in nude mice and its influences on expressions of HIF-1α,GLUT-1,MMP-2.Methods: Lung cancer cells A549 were cultured and implanted subcutaneously into nude mice to establish an animal model of the human lung cancer xenograft.Tumor-bearing nude mice were randomly divided into three groups: HIF-1αASODN group, HIF-1αSODN group and the control group.HIF-1αASODN, HIF-1αSODN and normal saline were injected into subcutaneous tumors respectively once per three days for eight times. Take the intact subcutaneous tumor tissues, and then measure their volumes and their weight. Tumor growth inhibitory rate was calculated finally. Reverse transcription-polymerase chain reaction(RT-PCR) assay was performed to detect the expression levels of HIF-1α,GLUT-1,MMP-2 mRNA. Immunohistochemistry assay was performed to detect the expression levels of HIF-1α,GLUT-1,MMP-2 protein.Results: In HIF-1αASODN group, the subcutaneous tumors grew slowly and after treatment, the mean volume(319.31±15.12mm3)and mean weight(0.51±0.06g) were significantly different from HIF-1αSODN group(656.75±18.65mm3,0.97±0.11g) and the control group(678.03±19.67mm3,1.02±0.09g)(P<0.01). The tumor growth inhibitory rate was 50.00% in ASODN group. The expression levels of HIF-1α,GLUT-1,MMP-2 mRNA and protein in tumor tissues of ASODN group were obviously lower compared with SODN group and control group(P<0.01). The expression levels of HIF-1αmRNA were positively correlated with GLUT-1,MMP-2 mRNA(r1=0.437,P<0.01; r2=0.406,P<0.05) ;The expression levels of GLUT-1 mRNA also showed a positive correlation with MMP-2 mRNA(r=0.321, P<0.05). Conclusions: HIF-1αASODN, after injected into human lung carcinoma xenografts in nude mice, can inhibit the growth of subcutaneous tumors significantly and the expressions of HIF-1α,GLUT-1,MMP-2 in xenografts. The correlations among the expressions of HIF-1α,GLUT-1,MMP-2 in xenografts were positive obviously . HIF-1αcould regulate the expression of GLUT-1,MMP-2 positively.