title: A novel CRAd in combination with cisplatin enhanced the antitumor efficacy in ovarian cancer.
abstract: OBJECTIVE
  The aim of this study was to investigate the combined effects of a novel survivin promoter-based conditionally replicating adenovirus (CRAd-S.RGD) plus cis-diamminedichloroplatinum (cisplatin, CDDP) in ovarian cancer in vitro and in vivo.
  
  
  METHODS
  The viability of human ovarian cancer cell line SKOV3 was determined by MTT assay following the infection with different doses of CRAd-S.RGD, either alone or in combination with CDDP. The antitumor efficacies and survival curves were evaluated at the end of the treatment regimens with the subcutaneous administration of CRAd-S.RGD, CDDP, combined therapy of CRAd-S.RGD plus CDDP, or phosphate-buffered saline in a SKOV3 xenograft animal model. Furthermore, the apoptosis rate of tumor tissues in mice was determined subsequent to the treatments.
  
  
  RESULTS
  In vitro, the CRAd-S.RGD destroyed SKOV3 cells by oncolysis in a dose-dependent manner, and the viability of SKOV3 cells was significantly lower in the combined-therapy group than that in the individual-therapy groups. In vivo, enhanced tumor inhibition and animal survival rates were obtained in a synergistic manner with CRAd-S.RGD plus CDDP, as compared with the treatment with CRAd-S.RGD or CDDP alone. There was an increase in the apoptosis rate of the cells following the combined therapy. The results clearly demonstrated that there was a synergistic effect in the combination of CRAd-S.RGD and CDDP in increased therapeutic efficacy. Similar therapeutic efficacy could be obtained with CRAd-S.RGD plus CDDP at 2 lower doses that minimized the drug toxicity to host tissues.
  
  
  CONCLUSIONS
  The strategy of CRAd-S.RGD in combination with CDDP was a potential therapeutic modality for the therapy in ovarian cancer.
  
  
  BACKGROUND
  CDDP - cisplatin, cis-diamminedichloroplatinum, CRAd - conditionally replicating adenovirus, CRAd-survivin - the survivin promoter-based conditionally replicating adenovirus, CRAd-S.RGD - CRAd-survivin-RGD4C, MOI - multiplicity of infection, PBS - phosphate-buffered saline, PI - propidium iodide.
authors.affiliation: Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Jiangsu, China. beizhangxz@gmail.com
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Liu
authors.forename: Peiying
authors.initials: P
authors.lastname: Zhang
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wei
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000260:Adenoviruses, Human / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics; D050130:Oncolytic Virotherapy / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy* / Q000821:virology; D011897:Random Allocation; D000077022:Survivin; D014779:Virus Replication / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D000077022:Survivin; C047981:arginyl-glycyl-aspartic acid; D002945:Cisplatin