title: An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells.
abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China. Electronic address: liuranyi@mail.sysu.edu.cn.
authors.forename: Ran-Yi
authors.initials: RY
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
authors.forename: Bi-Jun
authors.initials: BJ
authors.lastname: Huang
authors.forename: Miao-la
authors.initials: ML
authors.lastname: Ke
authors.forename: Jie-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Fu
authors.forename: Jiang-Xue
authors.initials: JX
authors.lastname: Wu
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002277:Carcinoma; D043169:Endostatins / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D043169:Endostatins; D011994:Recombinant Proteins
keywords: Adenovirus vector; Endostatin; Nasopharyngeal carcinoma; Oncolytic virus; Viral-gene therapy