title: Enforced effect of tk-MCP-1 fusion gene in ovarian cancer.
abstract: OBJECTIVE
  The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo.
  
  
  METHODS
  A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot was performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were compared to those of SKOV3 expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene.
  
  
  RESULTS
  The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes.
  
  
  CONCLUSIONS
  These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Ji'nan 250012, People's Republic of China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Hong
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Fengnian
authors.initials: F
authors.lastname: Rong
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000276:immunology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015514:Oncogene Proteins, Fusion; D013937:Thymidine Kinase