title: Therapeutic efficacy by targeting correction of Notch1-induced aberrants in uveal tumors.
abstract: There is a need for more effective treatments for uveal melanoma. The recombinant oncolytic adenovirus H101 replicates specifically in p53-depleted tumor cells, and has been approved for use by the Chinese State Food and Drug Administration. However, this treatment is associated with subsequent remission. Transfection of uveal melanoma cells with a small interfering RNA against Notch1 (siNotch1) effectively suppressed Notch1 expression, resulting in significant cell growth inhibition when combined with H101 treatment. Combined treatment with siNotch1 and H101 (H101-Notch1-siRNA) greatly enhanced apoptosis and cell cycle arrest in vitro as compared to treatment with H101 or siNotch1 alone. For in vivo treatments, the combined treatment of siNotch1 and H101 showed remarkable tumor growth inhibition and prolonged mouse survival in the OCM1 xenograft model. We predict that Notch pathway deregulation could be a feature of uveal melanoma, and could be a therapeutic target, especially if p53 is concurrently targeted.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Guanxiang
authors.initials: G
authors.lastname: Qian
authors.forename: Jifan
authors.initials: J
authors.lastname: Hu
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D051881:Receptor, Notch1 / Q000235:genetics*; D015398:Signal Transduction; D014604:Uveal Neoplasms / Q000235:genetics / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering; D051881:Receptor, Notch1