title: Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma.
abstract: Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University; Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University.
authors.forename: Hang
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University.
authors.forename: Meng
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Mao
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D020382:Interleukin-18; D042461:Vascular Endothelial Growth Factor A; D003606:Dacarbazine
keywords: IL-18; dacarbazine; melanoma; oncolytic adenovirus