Figure 4: PDE10A inhibition attenuates ovarian xenograft tumor growth in nude mice.

A2780 cells with expression of luciferase were injected into flanks of female nude mice at the age of 6 weeks. 10 days post-inoculation of the tumor cells, the animals received the injection of saline, DOX (1.5mg/kg/day), TP-10 (succinate form, 4.5 mg/kg/day) (please note that we increased the mass of TP-10 succinate because its higher molecular weight (MW: 1301) compared to the free base form (MW: 1003)), or DOX plus TP-10 daily for 2 weeks. (A) Experiment timeline. (B) PDE10A protein levels measured by western blotting in A2780 xenografts from nude mice treated with vehicle, DOX, TP-10, or DOX plus TP-10, bar graph shows the average of n = 6 in each group. (C) Representative bioluminescence imaging after transplantation of A2780 cells. Mice were imaged at indicated days. (D) Line graphs showing the inhibitory effects of DOX, TP-10, or both on the growth of xenograft tumors. Tumor growth of A2780 xenografts was determined by caliper measurement over 2 weeks, n = 10–15 tumors per treatment group. (E) Photographs of the excised tumors at the end of the study (2 weeks after drug treatment). (F) Weights of excised tumors were determined at the end of study (2 weeks after drug treatment), n = 8–12 tumors per treatment group. Data were represented as mean ± SEM. Statistics: Welch ANOVA with Dunnett’s T3 corrections for 3 comparisons in A and for 4 comparisons in F, repeated measures ANOVA with Holm-Sidak post-hoc test for 5 comparisons at day 13 in D.