Inhibition of hypoxia inducible factor 1alpha by siRNA-induced apoptosis in human retinoblastoma cells.
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Gao Y, Jing M, Ge R, Zhou Z, Sun Y
Inhibition of hypoxia inducible factor 1alpha by siRNA-induced apoptosis in human retinoblastoma cells.
J Biochem Mol Toxicol. 2014 Sep;28(9):394-9. doi: 10.1002/jbt.21576. Epub 2014 May 23.
- PubMed ID
- 24860939 [ View in PubMed]
- Abstract
Hypoxia, which activates the hypoxia inducible factor 1alpha (HIF-1alpha), is an essential feature of retinoblastoma (RB) and contributes to poor prognosis and resistance to conventional therapy. In this study, the effect of HIF-1alpha knockdown by small interfering RNA (siRNA) on cell proliferation, apoptosis, and apoptotic pathways of human Y-79 RB cells was first investigated. Exposure to hypoxia induced the increased expression of HIF-1alpha both in mRNA and protein levels. Then, knockdown of HIF-1alpha by siRNAHIF-1alpha resulted in inhibition of cell proliferation and induced cell apoptosis in human Y-79 RB cells under both normoxic and hypoxic conditions, with hypoxic conditions being more sensitive. Furthermore, knockdown of HIF-1alpha could enhance hypoxia-induced slight increase of Bax/Bcl-2 ratio and activate caspase-9 and caspase-3. These results together indicated that suppression of HIF-1alpha expression may be a promising strategy for the treatment of human RB in the future.