肿瘤特异性表达shVEGF和自杀基因作为食管癌治疗的新策略。
Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.
作者信息
Liu Ting, Wu Hai-Jun, Liang Yu, Liang Xu-Jun, Huang Hui-Chao, Zhao Yan-Zhong, Liao Qing-Chuan, Chen Ya-Qi, Leng Ai-Min, Yuan Wei-Jian, Zhang Gui-Ying, Peng Jie, Chen Yong-Heng
机构信息
Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
出版信息
World J Gastroenterol. 2016 Jun 21;22(23):5342-52. doi: 10.3748/wjg.v22.i23.5342.
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/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.
目的
开发一种有效且安全的食管癌基因治疗方法。
方法
构建携带融合自杀基因（yCDglyTK）和针对血管内皮生长因子（VEGF）的短发夹RNA（shRNA）的表达载体，并通过磷酸钙纳米颗粒（CPNP）将其导入EC9706食管癌细胞。为实现肿瘤选择性，融合自杀基因的表达由肿瘤特异性人端粒酶逆转录酶（hTERT）启动子驱动。在存在前体药物5-氟胞嘧啶（5-FC）的情况下，对该载体的生物学特性和治疗效果进行体内外评估。
结果
体内外测试均表明，CPNP能有效地将表达载体导入肿瘤细胞，导致yCDglyTK在细胞中表达，并降低VEGF水平。在接触5-FC后，它对食管癌表现出强大的抗肿瘤作用。VEGF shRNA与融合自杀基因联合显示出强大的抗肿瘤活性。
结论
shVEGF-hTERT-yCDglyTK/5-FC系统为食管癌靶向基因治疗提供了一种新方法。
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