title: E10A, an adenovirus carrying human endostatin gene, in combination with docetaxel treatment inhibits prostate cancer growth and metastases.
abstract: 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 tumor growth inhibition and survival improvement. The antitumoral effect was tightly correlated with a remarkable decrease in tumor 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wu
authors.forename: Fajun
authors.initials: F
authors.lastname: Xie
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Ranyi
authors.initials: R
authors.lastname: Liu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D000077143:Docetaxel; D043169:Endostatins / Q000235:genetics* / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000628:therapy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D043823:Taxoids / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D043823:Taxoids; D000077143:Docetaxel