title: Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24.
abstract: OBJECTIVE
  The aim of this study was to creatively implement a novel chemo-gene-virotherapeutic strategy and further strengthen the antitumor effect in cancer cells by the combined use of ZD55-IL-24 and cisplatin.
  
  
  METHODS
  ZD55-IL-24 is an oncolytic adenovirus that harbors interleukin 24 (IL-24), which has a strong antitumor effect and was identified and evaluated by PCR, RT-PCR, and Western blot analysis. Enhancement of cancer cell death using a combination of ZD55-IL-24 and cisplatin was assessed in several cancer cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cytopathic effect (CPE) assay. Apoptosis induction by treatment with ZD55-IL-24 and/or cisplatin was detected in BEL7404 and SMMC7721 by morphological evaluation, apoptotic cell staining, and flow cytometry analysis. In addition, negative effects on normal cells were evaluated in the L-02 cell line using the MTT assay, the CPE assay, morphological evaluation, apoptotic cell staining, and flow cytometry analysis.
  
  
  RESULTS
  The combination of ZD55-IL-24 and cisplatin, which is superior to ZD55-IL-24, cisplatin, and ZD55-EGFP, as well as ZD55-EGFP plus cisplatin, resulted in a significantly increased effect. Most importantly, conjugation of ZD55-IL-24 with cisplatin had toxic effects equal to that of cisplatin and did not have overlapping toxicities in normal cells.
  
  
  CONCLUSIONS
  This study showed that ZD55-IL-24 conjugated with cisplatin exhibited a remarkably increased cytotoxic and apoptosis-inducing effect in cancer cells and significantly reduced the toxicity in normal cells through the use of a reduced dose.
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Yu-mei
authors.initials: YM
authors.lastname: Wu
authors.forename: Kang-jian
authors.initials: KJ
authors.lastname: Zhang
authors.forename: Xue-tian
authors.initials: XT
authors.lastname: Yue
authors.forename: Yi-qiang
authors.initials: YQ
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Gong-chu
authors.initials: GC
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Yi-gang
authors.initials: YG
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D000099180:Interleukin-24
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D007378:Interleukins; D000099180:Interleukin-24