Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy
Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy
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shVEGF 和自杀基因的肿瘤特异性表达作为食管癌治疗的新策略
DOI：
10.3748/wjg.v22.i23.5342
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发表时间：
2016-06-21
影响因子：
4.3
通讯作者：
Chen, Yong-Heng
中科院分区：
文献类型：
--
作者：
Liu, Ting;Wu, Hai-Jun;Chen, Yong-Heng
目的：开发一种有效、安全的食管癌基因治疗方法。方法：构建融合自杀基因（yCDglyTK）和抗血管内皮生长因子（VEGF） shRNA的表达载体，通过磷酸钙纳米颗粒（CPNP）转染EC9706食管癌细胞。为了实现肿瘤选择性，融合自杀基因的表达是由肿瘤特异性人类端粒酶逆转录酶（hTERT）启动子驱动的。在前药5-氟胞嘧啶（5-FC）存在的情况下，对载体的生物学特性和治疗效果进行了体外和体内评价。结果：体外和体内实验均表明，CPNP将表达载体有效导入肿瘤细胞，导致yCDglyTK在细胞内表达，VEGF水平降低。5-FC暴露后，对食管癌表现出较强的抗肿瘤作用。VEGF shRNA与融合自杀基因的结合显示出较强的抗肿瘤活性。结论：shVEGF-hTERT-yCDglyTK/5FC系统为食管癌靶向基因治疗提供了新的途径。
AIM: To develop a potent and safe gene therapy for esophageal cancer.METHODS: An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA 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 (hTERT) 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 yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity.CONCLUSION: The shVEGF-hTERT-yCDglyTK/5FC system provided a novel approach for esophageal cancer-targeted gene therapy.