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    FIGURE 4 from Inhibition of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition in Melanoma Tumors and May Improve Immunotherapy Efficacy by Reducing T-cell Exhaustion

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    Functional differences between celecoxib and CAY10678 and the impact of CAY10678 on tumor growth in mice. A, Release of PGE2 in supernatants in murine BrafV600E melanoma cells (left) and human WM793 cells (right) treated with different concentrations (0, 5, and 10 μmol/L) of celecoxib and CAY10678, measured by ELISA (n = 4). B, Proliferation assay of murine BrafV600E melanoma cells. Cells were treated with different concentrations of celecoxib and CAY10678 (0, 5, and 10 μmol/L). Cell viability was assessed at 0, 24, 48, and 72 hours. Results represent the fold change relative to the OD value of each group prior to treatment (n = 6). Differences between two groups were analyzed by repeated measures one-way ANOVA, followed by Tukey post hoc test. C, Shown are results of qRT-PCR analyses for col3a1, col4a1, col4a2, col8a1, col16a1, and col18a1 genes in murine BrafV600E melanoma cells treated with 0.1% DMSO, 10 μmol/L celecoxib, or 10 μmol/L CAY10678 for 24 hours. Bar graphs show the fold change relative to mRNA levels of control (0.1% DMSO) for each gene (n = 4). D, Left, Tumor volume at indicated timepoints for murine BrafV600E melanoma cells. A total of 1 × 106 cells per mouse were injected subcutaneously into the flanks of C57BL/6J mice. The tumor-bearing mice were randomly assigned into two groups on day 8: vehicle (n = 5) and CAY10678 (n = 7) groups. Mice in the CAY10678 group were treated with intraperitoneal injection of 100 mg/kg CAY10678 daily. D, Right, Tumor volume for individual mice in each treatment group. E, Mice were euthanized on day 21, and the tumors were weighed. F, PGE2 levels in tumors were measured by ELISA. G, Chronologic changes in body weight in the two groups. Graph values represent mean ± SD. Significance in difference between two groups was tested by Student t test. Differences in tumor volume and body weight were analyzed by repeated measures one-way ANOVA followed by Tukey post hoc test. **, P P < 0.05. N.S., not statistically significant.</p
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