PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells

摘要: Overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) in human tumors is associated with poor prognosis and outcome to radiation therapy. Inhibition HIF-1alpha considered as a promising approach cancer The purpose this study was test the efficacy novel inhibitor PX-478 radiosensitizer under normoxic hypoxic conditions vitro. PC3 DU 145 prostate carcinoma cells were treated for 20 hr, protein level clonogenic cell survival determined normoxia hypoxia. Effects on cycle distribution phosphorylation H2AX histone evaluated. decreased cells. produced cytotoxicity both lines enhanced toxicity hypoxia DU-145. (20 mumol/L) radiosensitivity irradiated condition enhancement factor (EF) 1.4 1.56, respectively. drug less effective inhibiting enhancing compared EF 1.13 (normoxia) 1.25 (hypoxia) at 50 mumol/L concentration. induced S/G2M arrest but not Treatment resulted prolongation gammaH2AX expression now undergoing Phase I clinical trials an oral agent. Although precise mechanism remains be identified, suggests potential role enhancer.