title: [Anti-nasopharyngeal carcinoma effect in vivo and in vitro of Avastin and adenovirus-thymidine kinase suicide gene].
abstract: OBJECTIVE
  To evaluate the effect of Avastin and adenovirus-thymidine kinase/ Ganciclovir (Ad-TK/GCV) suicide gene system on nasopharyngeal carcinoma in vivo and in vitro.
  
  
  METHODS
  The expression of vascular endothelial growth factor (VEGF) by CNE1 cell line was detected by VEGF ELISA. The effect of Avastin and Ad-TK/GCV on CNE1 cell was detected by methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and Hoechst 33342 staining were adopted to explore the killing mechanism of Ad-TK/GCV. The nude mice models of CNE1 cell xenografts were established. After intra-tumoral injection of PBS, Avastin, Ad-TK/GCV, Ad-Lac-Z/GCV and Ad-TK/GCV + Avastin, tumor volume was measured and tumor inhibitory rate was calculated. Then the tumors were removed and subjected to histological examination.
  
  
  RESULTS
  CNE1 cells could produce VEGF. Avastin had no direct effect on CNE1 cells. The killing effect of Ad-TK/GCV increased with the increase of Ad-TK multiple of infection and the prodrug concentration, which was enhanced by the existence of bystander effect. Compared with control group, the death cell rate (P = 0.000) and apoptosis cell rate (P = 0.000) had significant difference. The study in vivo showed the tumors treated with Avastin, Ad-TK/GCV and Ad-TK/GCV + Avastin grew slowly compared with control. Tumor volume of treated groups was significantly smaller than that of control (all P < 0.05 or P = 0.000). Tumor weight of treated groups was significantly lower than that of control (all P = 0.000). The histological examination showed local necrosis in Ad-TK/GCV group and Ad-TK/GCV + Avastin group, poor angiogenesis in Avastin group and Ad-TK/GCV + Avastin group.
  
  
  CONCLUSIONS
  Avastin had no direct effect on CNE1 cells in vitro. Ad-TK/GCV suicide gene system killed NPC cells by inducing cell necrosis and apoptosis, which could be enhanced by the existence of bystander effect. Avastin and Ad-TK/GCV suicide gene system could inhibit the growth of NPC CNE1 cell xenografts. Combination therapy had a synergic effect.
authors: Cancer Center, Shandong Provincial Hospital, Jinan 250021, China. sharrysha@yahoo.com.cn
authors: Dan
authors: D
authors: Sha
authors: You-jian
authors: YJ
authors: He
authors: Wei-bo
authors: WB
authors: Wang
authors: Jun-qing
authors: JQ
authors: Han
mesh_terms: D000256:Adenoviridae / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005260:Female; D015774:Ganciclovir; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D013937:Thymidine Kinase; D015774:Ganciclovir