title: Combination of oncolytic adenovirus and dacarbazine attenuates antitumor ability against uveal melanoma cells via cell cycle block.
abstract: Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the viro-chemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.
authors.affiliation: Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Cun
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003588:Cytopathogenic Effect, Viral; D003606:Dacarbazine / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D013997:Time Factors; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000628:therapy*; D014779:Virus Replication / Q000187:drug effects; D000098943:Uveal Melanoma
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine