Figure 5. HIF-1α regulates the ADAM9 expression under hypoxic condition.
(A) Hypoxia dependent ADAM9 protease activity was decreased when cells were treated with HIF-1α siRNA under hypoxic condition. HIF-1α siRNA and RAV-18 combined to inhibited ADAM9 protease activity more than HIF-1α siRNA treatment alone (*; p < 0.05). NMX; Normoxia, HPX; Hypoxia, siHIF; siRNA against HIF1α and RAV; RAV-18 (B) Cell proliferation was increased in low ADAM9 cells under hypoxic condition and decreased by HIF-1α siRNA transfection of cells, (*; p < 0.05). N-C; Control on Normoxia, H-C; control on Hypoxia, H-N; negative siRNA on Hypoxia, H-H; siRNA against HIF1α on hypoxia, H-R; RAV-18 on hypoxia and H-H-R; combination of siHIF1α and RAV-18 on hypoxia (C) Increased expression of HIF-1α as well as ADAM9 and its down-stream signaling was inhibited by HIF-1α siRNA transfection. When HIF-1α siRNA and RAV-18 were used in combination, HIF-1α expression was not changed comparing to HIF-1α siRNA treatment alone. However, phospho-EGFR and phosph-ERK expression were decreased more than HIF-1α siRNA treatment alone. Phospho-AKT expression was not changed when HIF-1α siRNA, with or without RAV-18 was used. N; negative siRNA and H; siRNA against HIF1α