Figure 6

Effects of KYA1797K on lung tumorigenesis and on the Wnt/β-catenin and the Ras-ERK pathways in erlotinib-resistant Kras^LA2 mice. (A–F) Kras^LA2 mice were treated for 7 weeks by oral gavage with 25 mg/kg erlotinib 5 days a week for 7 weeks (4 mice for vehicle and 6 mice for erlotinib), or by intraperitoneal injection with 25 mg/kg KYA1797K 6 days a week for 7 weeks (7 mice for vehicle and 7 mice for KYA1797K). (A) H&E staining images of lung tumors (arrows) in mice treated with erlotinib or with KYA1797K. (B,C) The number of tumors in mice treated with erlotinib (B) or KYA1797K (C) were counted separately based on size. Tumors which sizes are less than 1 mm are counted as small, 1–3 mm as medium and greater than 3 mm as large. Error bars represent the SD; ^*P < 0.05, ^**P < 0.01, ^***P < 0.001; n = 4 (vehicle), 6 (erlotinib) (B) or n = 7 (vehicle), 7 (KYA1797K) (C). (D) Immunohistochemical of the downstream effectors of the Wnt/β-catenin and the Ras-ERK pathways in the lung tumor regions from mice treated with erlotinib or KYA1797K. Nuclei were counter stained with DAPI. Scale bars, 20 μm. (E,F) WCLs of lung tumors of mice treated with erlotinib (E) or KYA1797K (F) were subjected to the immunoblot analyses using indicated antibodies.