E10A, an adenovirus carrying human endostatin gene, in combination with docetaxel treatment inhibits prostate cancer growth and metastases

摘要

E10A, a replication-defective adenovirus carrying human endostatin gene, has finished Phase I clinical trials for solid cancers. We assessed whether the combination of E10A with docetaxel would enhance antiangiogenic activities and inhibit prostate cancer growth and metastases. Combination use of conditioned medium from prostate cancer cells infected by E10A and docetaxel exerted synergistic inhibition of HUVECs proliferation, migration and tube formation, compared with either agent alone. In prostate cancer s.c. xenograft models, combined therapy resulted in significant tumour growth inhibition and survival improvement. The antitumoural effect was tightly correlated with a remarkable decrease in tumour cell proliferation, microvessel, especially immature vasculature and significant increase in apoptosis induction. Systemic administration of E10A and docetaxel also effectively inhibited orthotopic growth and metastases of prostate cancer and achieved better in vivo antiangiogenic effects than either agent alone. Our data indicate that E10A in combination with docetaxel exert enhanced antiangiogenic activities and inhibit prostate cancer growth and metastases. Therefore, this approach may be an effective treatment for advanced prostate cancer and deserves more extensive investigation.