Biochimie
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The transcription factor hypoxia-inducible factor-1 (HIF-1) is an important regulator of the tumor response to hypoxia, including increased angiogenesis, glycolytic metabolism, and resistance to apoptosis. In the current study, small interfering RNA (siRNA)-mediated knockdown of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) suppressed hypoxia-induced stimulation of HIF-1α protein expression in PC3 human prostate cancer cells. ⋯ Inactivation of the phosphoinsotide-3 kinase (PI3K)/Akt pathway decreased HIF-1α expression through inactivation of Sp1. Thus, IDPm siRNA functioned as a potentially useful agent for targeting chemo- and radio-resistant hypoxic cells within solid tumors through inhibition of HIF-1α expression.