TNF-related Apoptosis-inducing Ligand Delivered by rNDV is a Novel Agent for Cancer Gene Therapy
TNF-related Apoptosis-inducing Ligand Delivered by rNDV is a Novel Agent for Cancer Gene Therapy
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DOI：
10.7785/tcrt.2012.500446
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发表时间：
2015-12-01
影响因子：
2.8
通讯作者：
Li, De-Shan
中科院分区：
文献类型：
--
作者：
Bai, Fu-Liang;Tian, Hui;Li, De-Shan
重组新城疫病毒（rNDV）作为抗肿瘤药物已被证明是有效的肿瘤治疗药物。tnf相关的凋亡诱导配体（TRAIL）也已被证明具有潜在的癌症治疗作用。在本研究中，我们构建了rNDV递送的TRAIL (rNDV-TRAIL)，并研究TRAIL是否会与rNDV产生潜在的协同治疗作用。体外实验表明，rNDV表达的TRAIL具有良好的生物活性。TRAIL在表达死亡受体的癌细胞中显著增强rNDV诱导凋亡的作用。在患有恶性黑色素瘤的小鼠中进行的实验表明，与对照组相比，rNDV传递的TRAIL的表达显著抑制了肿瘤的生长，延长了治疗动物的生存期。综上所述，TRAIL增强了rNDV的溶瘤能力，治疗性TRAIL基因的引入增强了NDV固有的抗肿瘤特性。
Recombinant Newcastle disease virus (rNDV) as antitumor agent has been shown to be effective for cancer therapy. And TNF-related apoptosis-inducing ligand (TRAIL) also has been demonstrated potentially cancer-therapeutic effects. In this study, we constructed TRAIL delivered by rNDV (rNDV-TRAIL) and investigated whether TRAIL would generate the potential synergistic therapeutic effects with rNDV for cancer therapy. In vitro experiments indicated that TRAIL expressed by rNDV demonstrated good biological activity. TRAIL significantly enhanced inducing apoptosis of rNDV in death receptor expression cancer cell lines. Experiments in malignant melanoma-bearing mice demonstrated that expression of TRAIL delivered by rNDV significantly inhibited the tumor growth and prolonged the survival of treated animals compared to control. In conclusion, oncolytic capacity of rNDV was augmented by TRAIL and the inherent anti-neoplastic properties of NDV were enhanced by the introduction of therapeutic TRAIL gene.