FIGURE 6.

36245-PHF inhibits tumor growth in both gefitinib-sensitive and -resistant NSCLC xenograft mouse models. Treatment with 36245-PHF significantly inhibits tumor growth in the gefitinib-resistant A549 xenograft mouse model (A) or gefitinib-sensitive HCC827 xenograft mouse model (B) versus the vehicle- or gefitinib-treated group. For each xenograft mouse model, athymic nude mice were divided into four groups as described under “Experimental Procedures.” Mice (n = 10) were treated by daily oral gavage with vehicle (□), 150 mg/kg gefitinib (○), 40 mg/kg 36245-PHF (■), or 200 mg/kg 36245-PHF (●). All data are represented as means ± S.D., and significant differences were determined by factorial analysis of variance (**, p < 0.01 versus vehicle). Representative photographs show external appearance of tumors. C, immunohistochemical (IHC) staining of Ki-67, phosphorylated (p)-Akt, and p-histone H3 in tumors formed in mice treated with vehicle, 150 mg/kg gefitinib, or 200 mg/kg 36245-PHF. Representative photographs for each antibody and each group are shown. The integrated optical density (IOD) was evaluated using the Image-Pro Plus software (version 6.2) program. (**, p < 0.01 versus vehicle).