title: Combined treatment with an oncolytic adenovirus and antitumor activity of vincristine against retinoblastoma cells.
abstract: Treatment trends of retinoblastoma (RB) have gradually evolved from eye enucleation and external radiation to local treatment. Combined treatment with an oncolytic virus and chemotherapy is currently a new method in RB treatment. To investigate the therapeutic effect of oncolytic adenovirus SG600 in combination with vincristine (VCR) on retinoblastoma in vitro, the cell viability, cell cycle effects and apoptotic activity of HXO-RB(44) cells treated with SG600, VCR or SG600 plus VCR were measured using a cell counting kit-8-based procedure and flow cytometry. Western blot analysis for Akt, p-Akt, p-p53 and p-Rb protein was performed to investigate the underlying mechanisms of combined therapy. The combination therapy exerted a synergistic antitumor effect via a type of G(2)/M and S phase arrest rather than the induction of apoptosis. The combination of VCR and SG600 further reduced Akt phosphorylation compared with cells treated with VCR alone, suggesting that SG600 could overcome chemoresistance, perhaps by down-regulating Akt in RB cells. An increase in the expression of p-p53 and decrease in p-Rb expression in HXO-RB(44) after co-treatment might be associated with cell cycle block. Western blot examination revealed that VCR might enhance SG600 replication. These results suggest that viro-chemo combination therapy is a feasible and potentially promising approach for the treatment of retinoblastoma.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Cun
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Guanxiang
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.|Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019572:Retinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014750:Vincristine / Q000627:therapeutic use*; D014779:Virus Replication
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; drug resistance; oncolytic adenovirus; retinoblastoma; vincristine