Fig. 4.

Inhibition of mPGES-1 and its impact on tumor growth in a preclinical neuroblastoma mouse model. (a) Schematic overview of an in vivo xenograft experiment: 1. Mice were injected with the human 11q-deleted cell line SK-N-AS (n = 30, 10⁶ cells) and randomized into daily CIII-treatments from the day of injection (n = 10, CIII-ET) or left untreated (n = 20, CTRL). 2. At tumor take (200 mm³) the control animals were randomized to daily CIII-treatment (n = 10, CIII) or left untreated (n = 10, CTRL). 3. Animals in all three groups were followed until sacrifice 9 days post tumor take. (b) Kaplan-Meier analysis of tumor development comparing tumor free (<1.0 ml) survival probability from tumor cell injection, of CIII treated mice (CIII-ET) or untreated mice (CTRL), (P = 0.0094, Log-rank test (Mantel-Cox)). (c) Effect of daily CIII-treatment (9 consecutive days after tumor take, n = 9) on established tumors compared to untreated tumors (n = 10). Data is represented as mean tumor volume (calculated as (width)² × length × 0.44) ± SEM, day 4–9 P < 0.05, unpaired t-test). (d) Weight of tumors and representative image (e) of mice at the day of sacrifice (9 days post tumor take) from mice receiving treatment from the day of injection (P = 0.022, CIII-ET), from mice receiving treatment from tumor take (P = 0.019, CIII) compared to untreated mice (CTRL), unpaired t-test. Data is represented as a Box and whiskers plot showing minimum to maximum range and each mouse as an individual data point. (f) Quantification of immunohistochemical Ki-67 staining in SK-N-AS xenograft tumors from at least four mice in each group. Data is presented as mean ± SEM and P-value calculated using unpaired t-test.