AIM: To develop a potent and safe gene therapy for esophageal cancer.METHODS: An expression vector carrying fusion suicide gene(y CDgly TK) and sh RNA against vascular endothelial growth factor(VEGF) was constructed a...AIM: To develop a potent and safe gene therapy for esophageal cancer.METHODS: An expression vector carrying fusion suicide gene(y CDgly TK) and sh RNA against vascular endothelial growth factor(VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles(CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase(h TERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine(5-FC), were evaluated in vitro and in vivo.RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of y CDgly TK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF sh RNA with the fusion suicide gene demonstrated strong anti-tumor activity.CONCLUSION: The sh VEGF-h TERT-y CDgly TK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.展开更多
基金Supported by National Natural Science Foundation of ChinaNo.81372904+3 种基金No.81272971No.81272735 and No.30800518Science and Technology Department of Hunan ProvinceNo.2010CK3013
文摘AIM: To develop a potent and safe gene therapy for esophageal cancer.METHODS: An expression vector carrying fusion suicide gene(y CDgly TK) and sh RNA against vascular endothelial growth factor(VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles(CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase(h TERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine(5-FC), were evaluated in vitro and in vivo.RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of y CDgly TK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF sh RNA with the fusion suicide gene demonstrated strong anti-tumor activity.CONCLUSION: The sh VEGF-h TERT-y CDgly TK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.
