Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling (original) (raw)
Figure 4
Anti-inflammation delays SCC development and prolongs survival of Tgfbr2fspKO mice.
(A) Kaplan survival curve of Tgfbr2fspKO mice treated with Celecoxib or housed in Helicobacter free environment. The pups received the Celecoxib starting the second week after birth, together with the nursing mother mouse in the same cage. The treatment continued after weaning. (B) Celecoxib-treated and Helicobacter free Tgfbr2fspKO mice displayed decreased hyperplasia and CD45+ infiltration by histopathology compared to untreated Tgfbr2fspKO mice. Forestomach samples from 5 week mice stained for H&E and CD45. Scale bar: 20 µm. (C) Western blot analysis of iNOS, COX2, p65, γ-H2AX and p53 in forestomach samples from Tgfbr2fspKO mice treated with Celecoxib or L-NAME. (D) IFN-γ and TNF-Bioplex assay with forestomach samples from Tgfbr2fspKO and Tgfbr2fspKO mice treated with Celecoxib or housed in Helicobacter free condition. Error bars represent SD. **P<0.01 and ***P<0.001. (E) Reduced production of 8-oxo-dG in Tgfbr2fspKO mice treated with Celecoxib or in Helicobacter free conditions. Scale bar: 20 µm.