title: Additive antitumoral effect of interleukin-12 gene therapy and chemotherapy in the treatment of urothelial bladder cancer in vitro and in vivo.
abstract: BACKGROUND
  We evaluated antitumoral effect of combined chemotherapy and interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental urothelial bladder cancer (UBC) model.
  
  
  METHODS
  EJ UBC cells were transfected with recombinant IL-12 genes using a liposomal transfection agent. Pirarubicin (THP) was added to the experimental samples at a final concentration of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected cells, untransfected cells plus THP and transfected cells plus THP. Death rates (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model was established by subcutaneous injection of EJ cells to the nude mice. Four groups were assigned in vivo: control group; THP group; IL-12 gene group and IL-12 gene plus THP group. After injection of combined THP and IL-12 gene therapy, tumor size and IL-12 levels were evaluated.
  
  
  RESULTS
  In vitro study: DR in the THP + IL-12 gene therapy group (58.2 ± 15.8%) was significantly higher than transfected group (12.2 ± 5.6%; P = 0.01) and untransfected cells plus THP group (33.4 ± 7.8; P = 0.046). A higher amount of apoptotic changes and necrosis on transmission electron microscope analysis were observed in transfected cells plus THP group. In vivo study: A significant tumor attenuation was found in IL-12 gene in combination with THP group when compared with any other groups that were treated without Il-12 or THP (P < 0.05). IL-12 levels in serum were significant high in IL-12 gene groups (P < 0.01).
  
  
  CONCLUSIONS
  The combination of THP chemotherapy and IL-12 gene therapy showed an additive antitumoral effect on bladder cancer cells in vitro and in vivo. Further investigation should be focused on high-level transgene protocols in vivo.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str, Nangang District, 150001 Harbin, Heilongjiang, People's Republic of China.
authors.forename: Wanpeng
authors.initials: W
authors.lastname: Liu
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Cao
authors.forename: Mario I
authors.initials: MI
authors.lastname: Fernández
authors.forename: Haitao
authors.initials: H
authors.lastname: Niu
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Xiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D014162:Transfection; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy* / Q000648:ultrastructure
chemical_list: D000970:Antineoplastic Agents; D018664:Interleukin-12; D004317:Doxorubicin; C027260:pirarubicin