PHA665752 inhibits growth of TPC-1 xenograft and downregulates c-Met and its downstream signaling pathway in vivo. Nude mice at 6 wks of age were injected with 10 million MDAH2774 cells. (A) Effect of PHA665752 on TPC-1 xenograft. The volume of each tumor was measured every week. The average (n = 6) tumor volumes in vehicle-treated mice (
) and mice treated with indicated doses of TRAIL (25 μg/kg;
), PHA665752 alone (25 μg/kg;
) and a combination of TRAIL and PHA665752 (PHA665752 25 μg/kg + TRAIL 25 μg/kg; —●—) were plotted. The results are expressed as mean ± SD (n = 6). *P < 0.001 compared with vehicle-treated mice. (B) After 5 wks of treatment, mice were killed and tumor weights were measured. The results are expressed as mean ± SD. *P < 0.001 compared with vehicle-treated mice by Student t test. (C) Representative tumor images of vehicle-treated mice and mice treated with PHA665752 and/or TRAIL after necropsy. (D) Whole cell homogenates from mice treated with vehicle, 25 μg/kg TRAIL, 25 mg/kg PHA665752 and a combination of 25 μg/kg TRAIL and 25 mg/kg PHA665752 were immunoblotted with p-Met, p-AKT, caspase 3, cleaved caspase 3, PARP and β-actin antibodies.