Hif-1 Alpha Effects On Angiogenic Potential In Human Small Cell Lung Carcinoma

Background: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study aimed to investigate the effect of HIF-1 alpha on angiogenic potential of SCLC including two points: One is the effect of HIF-1 alpha on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1 alpha in vitro and in vivo.Methods: In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis.Results: In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM) was promoted after exogenous HIF-1 alpha transduction (p < 0.05). In vitro the changes of angiogenic genes expression induced by HIF-1 alpha in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1 alpha upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1 alpha in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated.Conclusions: These results indicated that HIF-1 alpha may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1 alpha may be a potential target for the gene targeted therapy of SCLC.