Inhibition of hypoxia inducible factor 1α by siRNA-induced apoptosis in human retinoblastoma cells.

Hypoxia, which activates the hypoxia inducible factor 1α (HIF-1α), is an essential feature of retinoblastoma (RB) and contributes to poor prognosis and resistance to conventional therapy. In this study, the effect of HIF-1α 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-1α both in mRNA and protein levels. Then, knockdown of HIF-1α by siRNAHIF-1α 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-1α 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-1α expression may be a promising strategy for the treatment of human RB in the future.