Hypoxia-Inducible Factor 1α Determines Gastric Cancer Chemosensitivity via Modulation of p53 and NF-κB
Figure 2
HIF-1α mediates resistance towards 5-FU by blocking p53-dependent G1 arrest and apoptosis.
(A) AGS KD and SCR cells were treated for 24 h with 10 µg/ml 5-FU, and cell cycle distribution was determined by FACS analysis (**, P<0.01). (B) Chemotherapy-induced senescence was quantified in AGS KD and SCR cells 4 days after treatment with 5-FU by measurement of SA-β-Gal activity (**, P<0.01). (C) AGS KD and SCR cells were treated for 48 h with 10 µg/ml 5-FU and apoptosis was quantitated based on detection of active caspase-3 using flow cytometry (**, P<0.01). (D) Representative immunoblot analysis of p53, p21, CDK2, cyclin A and pRb protein levels in AGS KD and SCR cells treated with 10 µg/ml 5-FU for 6 and 24 h. Actin served as loading control. ppRb, phosphorylated pRb.
