Figure 6.

Antitumoral activity of gefitinib and HDAC inhibitor combined treatment in vivo. (a) Effects of combined treatment with gefitinib and vorinostat on growth of H358 xenograft tumors in athymic nude mice. The mice were randomly assigned to one of four treatment groups. Group 1 (control mice) received vehicle, group 2 received gefitinib, group 3 received vorinostat, and group 4 received gefitinib and vorinostat. Gefitinib (5 mg/kg body weight) or vorinostat (100 mg/kg body weight) were administered orally 5 days/week. Tumor volumes were measured 3 times a week. Points, mean tumor volume (n = 8); bars, SE. *P < 0.05, **P < 0.01, for comparisons between treated and control for each serie of experiments. (b) Acetylated proteins and Ki67 nuclear protein detected by immunostaining on frozen tumor sections from control mice, mice treated with vorinostat, gefitinib or both gefitinib and vorinostat, as indicated. IgG, irrelevant antibody. Bars = 50 µm. Histogram: the percentage of positive cells for Ki67 was determined after counting stained cells per 1,000 cells on a section. Results are expressed as mean ± SD (n = 6 mice per group); **P = 0.0039 for comparisons between combined treatment and control or single treatment. (c) Effect of gefitinib and vorinostat on the expression of activated-caspase-3 in H358 xenograft tumors, assessed by western blotting. Actin was used as loading control.