Research Paper Volume 8, Issue 8 pp 1608—1624

A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts


Figure 7. The COX-2/PTEN axis regulates the pro-tumourigenic phenotype of senescent CAF. Senescent CAF/GU-OSCC (n=3) secreted more PGE2 than the non-senescent CAF/GS-OSCC (n=2) and normal fibroblasts (n=3), as assessed by ELISA (A). Cisplatin treatment increased PGE2 secretion by senescent CAF and normal fibroblasts (n=3) (B). Blockade of COX-2 catalytic activity diminished PGE2 secretion by normal fibroblasts and senescent CAF (n=3) (C). In contrast to normal fibroblasts (n=4), senescent-CAF (n=3) expressed less PTEN protein and this was rescued by celecoxib treatment (D). Celecoxib treated senescent CAF showed reduced capacity to stimulate paracrine migration of H357 cells in vitro, (n=3) (E). Celecoxib treatment abrogated activation of CAF and cisplatin-induced premature senescent fibroblasts by extenuating stress fibers formation visible as diminished fluorescence intensity (n=3) (F). All experiments were performed independently as indicated by n and with technical repeats. The bars represent mean ± SEM. *p<0.05, by Mann-Whitney U-test (A), two-way ANOVA with post-hoc correction by Bonferroni t-test (B-C) and Holm-Sidak method (E) and paired student's t-test (D).