[Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice]

Objective: To examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate Cancer in mice.

Methods: Thirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate Cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice.

Results: At 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P < 0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P < 0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental Animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P < 0.001).

Conclusion: EP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate Cancer in mice.