Treatment with siRNA and antisense oligonucleotides targeted to HIF-1α induced apoptosis in human tongue squamous cell carcinomas

摘要: Overexpression of hypoxia inducible factor-1α (HIF-1α) in cancers has been correlated to a more aggressive tumor phenotype. We investigated the effect HIF-1α knockout on vitro survival and death human tongue squamous cell carcinomas (SCC-4 SCC-9). Under normoxic condition, basal level protein was constitutively expressed SCC-9 cells, albeit an undetectable messages. Exposure induced only transient increase mRNA transcript but prolonged elevation its immediate downstream target gene product, VEGF. or hypoxic conditions, treatment cells with AS-HIF-1α ODN suppressed both constitutive hypoxia-induced expression at levels. Knockout via either siRNA (siRNAHIF-1α) resulted inhibition proliferation apoptosis SCC-4 cells. also demonstrated that exposure led time-dependent bcl-2 IAP-2, not p53. The attenuated levels enhanced activity caspase-3 after may contribute partly effects blockade death. Collectively, our data suggest is sufficient confer genes essential for survival. As result, interfering pathways by antisense strategy provide therapeutic carcinomas. © 2004 Wiley-Liss, Inc.