Tumor-specific expression of sh VEGF and suicide gene as a novel strategy for esophageal cancer therapy

• Published in: 世界胃肠病学杂志：英文版 no. 23; pp. 5342 - 5352
• Main Author: Ting Liu Hai-Jun Wu Yu Liang Xu-Jun Liang Hui-Chao Huang Yan-Zhong Zhao Qing-Chuan Liao Ya-Qi Chen Ai-Min Leng Wei-Jian Yuan Gui-Ying Zhang Jie Peng Yong-Heng Chen
• Format: Journal Article
• Language: English
• Published: 2016
• Subjects: cancer;Suicide; endothelial; Esophageal; factor;Nanoparticles; gene;RNA; growth; interference;Vascular
• ISSN: 1007-9327; 2219-2840

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.