1. NOX1-deficient mice do not respond to GKT771 and exhibit reduced tumor growth, angiogenesis, and lymphangiogenesis.
NOX1-deficient mice do not respond to GKT771 and exhibit reduced tumor growth, angiogenesis, and lymphangiogenesis. C57/BL6 and NOX1-deficient mice with established MC38 tumors were treated with GKT771 (n = 11), DC101 (n = 6), rat IgG (n = 6), or vehicle (n = 13). (A, B) Tumor size was measured in vivo using a caliper (D-0 to D-15) every 5 d. (C, D) Tumor size and mass were measured ex vivo at the end of the experiment. (E) Tumors from C57/BL6 and NOX1-deficient mice were isolated, and blood vascular endothelial cells (CD45−/CD31+/GP38−) and lymphatic endothelial cells (CD45−/CD31+/GP38+) were analyzed by flow cytometry (n = 13 and n = 11, respectively). The percentages of blood vascular cells and lymphatic endothelial cells in WT and KO mice are shown. (F) Aortic rings from WT and NOX1-deficient mice were stimulated with mouse rVEGF-A and exposed to GKT771 or DMSO as the negative control (n = 7). Branching areas were quantified and graphed. (G–I) Absolute numbers of blood endothelial cells (CD45−/CD31+/GP38−) (G), lymphatic endothelial cells (CD45−/CD31+/GP38+), (H) and macrophages (CD45+/CD11b+/F4-80+) in lungs and tumors (I) were determined after sorting by cytometry from WT or KO mice (n = 4). (J–L) Plasma of WT and KO mice bearing MC38 tumors treated with GKT771 or DMSO was used to quantify VEGF-A (J), PLGF (K), and VEGF-C (L) by ELISA.
Jimmy Stalin et al. LSA 2019;2:e
© 2019 Stalin et al.