Fig. 6
Inhibition of VCP suppresses the pro-metastatic effect of MEST. A, B MEST-overexpressing A549 and H1299 cells were treated with either 0.5 μM of CB-5083 or DMSO for 48 h and subjected to transwell assays to detect their invasion (A) and migration (B) abilities. Scale bar, 100 μm. C The NF-κB markers including p-IκBα, IκBα, p-p65, and p65 were determined by western blot analysis. D-F NCG mice were transplanted with luciferase-labeled cells that either with or without MEST overexpression (1 × 106 cells per mouse) via tail vein injection (n = 6). The indicated treatment group or control group was orally administered CB-5083 (30 mg kg−1) or vehicle, respectively, every 2 days. Mice were visualized 1.5 months after transplantation by using an IVIS 200 Imaging System (D). Lungs harvested after imaging are shown (E). Note that CB-5083 suppresses the metastatic nodules formed by MEST-overexpressing A549 cells in the lungs. Pulmonary metastases in the mouse model were histologically analyzed by H&E staining (F); scale bar, 100 μm