title: Experimental study of the RV-HSV-TK/GCV suicide gene therapy system in gastric cancer.
abstract: OBJECTIVE
  The aim of this study was to study in vitro and in vivo the killing effect and the bystander effect of herpes simplex virus-thymidine kinase gene/ganciclovir (HSV-TK/GCV) suicide gene system on the gastric cancer cell line, SGC-7901.
  
  
  METHODS
  GINaTK retroviral vector containing the HSV-TK gene was transduced into the PA317 packaging cell by lipofectin. The gastric cancer cell line, SGC-7901, was infected by a high-titer viral supernatant. SGC-7901/TK cells and SGC-7901 cells were used in the in vitro and in vivo studies. In the in vitro study, sensitivity of the SGC-7901/TK cells to GCV and the bystander effect were observated by a mononuclear cell direct cytotoxicity assay test. In the in vivo study, SGC-7901/TK cells and SGC-7901 cells were injected subcutaneously into the flanks of BALB/C nude mice, GCV was administrated intraperitoneally, a reverse transcriptase polymerase chain reaction was applied to detect the expression of the HSV-TK gene. A statistical analysis of the data was performed by using the analysis of variance.
  
  
  RESULTS
  The SGC-7901 cells transferred with the GINaTK gene displayed a higher antitumor effect than the parent cells. In the in vitro study, when the ratio of SGC-7901/TK cells reached 10%, the tumor cell-killing proportion was 53%. In the in vivo study, all BALB/C nude mice developed tumors in 7 days after tumor cells were implanted, the ratio of tumors formation is 100%. GCV could suppress tumor formation of the SGC-7901/TK cells. After the BALB/C nude mice treated with GCV, compared with the control tumors the median tumor volume of the mice implanted with SGC-7901/TK cells and BALB/C nude mice with cells mixed was, respectively, decreased to 52.8% and 69.4%.
  
  
  CONCLUSIONS
  The test showed that the HSV-TK gene can be transducted into the gastric cancer cell line, SGC-7901, under the mediation of a retrovirus and be stably expressed, and that the HSV-TK/GCV suicide gene therapy system could improve antitumoral efficiency. The bystander effect could be observated in the HSV-TK/GCV system both in vitro and in vivo.
authors.affiliation: School of Clinical Medical Science, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Qiusha
authors.initials: Q
authors.lastname: Tang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Meilin
authors.initials: M
authors.lastname: Wan
authors.forename: Liqiang
authors.initials: L
authors.lastname: Jin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D024201:Bystander Effect / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003587:Cytomegalovirus / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008979:Moloney murine leukemia virus / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir