BBR inhibited BBR inhibited HIF-1α/VEGF Raf/MEK/ERK and PI3K/AKT signaling.

<p>A549 cells were treated with BBR at the indicated doses. At 48 hours after treatment, the expression of HIF-1α, VEGF and PEDF at protein (<b>A</b>) or mRNA levels (<b>B</b>), as well as the total and phosphorylated Akt and ERK1/2 proteins (<b>D</b>), were determined. A549 cells were treated with the HIF-1α-specific siRNA (si-HIF) (<b>C</b>) or the Akt-selective inhibitor LY294002 (LY,30 µM) or the ERK-selective inhibitor U0126 (U, 50 µM) (E) for 24 hours, respectively, and then treated with BBR. At 48 hours after treatment, cell viability was determined by MTT analysis. The percent cell viability in each treatment group was calculated relative to cells treated with the vehicle control. The data are presented as the mean ± SD of three separate experiments. *, P < 0.05, significant differences between treatment groups and DMSO control groups.