Figure 7: Phospho-p38 and phospho-p44/42 MAPK signaling is increased in tumors from DOXO-treated mice.

(A-B) Representative IHC images of tumors from PBS + PBS: n =9, PBS + GCV: n=7, DOXO + PBS: n=11, DOXO + GCV: n=7, stained with p-p38 (A) or p-p44/42 (B) with the corresponding quantification of percent positive cells in the right panels. Shown are means ±SEM; *p<0.05, **p<0.01, (one-way ANOVA, Sidak’s multiple comparisons test was used post-analyses). (C-D) Representative IHC images of normal human skin and hSCC lesions (grades I-III) stained with p-p38 (C) and p-p44/42 (D). (E) Working model showing that DOXO induces senescence and a SASP in keratinocytes and fibroblasts, creating a microenvironment permissive for tumor growth and invasion. Once tumors are formed, senescent cells within the tumors also reinforce tumor growth by elevating p-p38 and p-p44/42 signaling.