Lung Cancer Mouse Models and Treatments

All animal care and experimental procedures were approved and conducted according to guidelines issued by the Vanderbilt University Institutional Animal Care and Use Committee. MerTK-KO mice on FVB background were provided by Dr. R. Cook (Vanderbilt University, Nashville, TN) [40 (link)]. Lung tumors were induced in IKKβ^Δmye mice (IKKβ^fl/fl; LysM-Cre) [41 (link)] and littermate WT controls by a single intraperitoneal (i.p.) injection of urethane (ethyl carbamate, 1 g/kg) (Sigma-Aldrich). BAY 11-7082 (10 mg/kg body weight; Cayman Chemical) was delivered by i.p. injection as described previously [27 (link)]. Warfarin (250mg/L, Sigma) was delivered with drinking water. Lung tumors were induced in LSL-Kras^G12D mice [42 (link)], using intratracheal (i.t.) instillation of adeno-Cre (1.5 × 10⁷ plaque-forming units). Subcutaneous tumors in C57BL/6 mice were established by an injection of 5 × 10⁵ syngeneic LLC cells in 100 ul of PBS in the right flank. When tumor size reached about 3 mm in diameter (day 6), mice were randomized and treated with vehicle control, BAY 11-7082 (10 mg/kg, i.p.,), Foretinib (30 mg/kg, gavage), or a combination of BAY 11-7082 and Foretinib every second day. Tumor sizes were measured using Traceable digital calipers (Fisher Scientific). Bronchoalveolar lavage (BAL) cells were collected and counted as previously described [12 (link)].