Molecular Biology Laboratory, Department of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar 243122, UP, India.
Appl Biochem Biotechnol. 2012 Aug;167(7):2005-22. doi: 10.1007/s12010-012-9700-1. Epub 2012 May 29.
Cancer is one of the killer diseases in humans and needs alternate curative measures despite recent improvement in modern treatment modalities. Oncolytic virotherapy seems to be a promising nonconventional way to treat cancers. Newcastle disease virus (NDV), a poultry virus, is nonpathogenic to human and domestic animals and has a long history of being used in oncotherapy research in several preclinical studies. The ability of NDV to successfully infect and destroy cancer cells is dependent on the strain and the pathotype of the virus. Adaptation of viruses to heterologous hosts without losing its replicative and oncolytic potential is prerequisite for use as cancer virotherapeutics. In the present study, velogenic NDV was adapted for replication in HeLa cells, and its cytotoxic potential was evaluated by observing morphological, biochemical, and nuclear landmarks of apoptosis. Our results indicated that the NDV-induced apoptosis in HeLa cells was dependent on upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and caspases activation. Different determinants of apoptosis evaluated in the present study indicated that this strain could be a promising candidate for cancer therapy in future.
癌症是人类的致命疾病之一,尽管现代治疗方法最近有所改善,但仍需要替代治疗方法。溶瘤病毒治疗似乎是一种有前途的非传统方法来治疗癌症。新城疫病毒(NDV)是一种禽类病毒,对人类和家畜无毒,并且在几种临床前研究中,在肿瘤治疗研究中已有很长的使用历史。NDV 成功感染和破坏癌细胞的能力取决于病毒的株系和病原型。为了将病毒用作癌症溶瘤疗法,病毒需要适应异源宿主而不丧失其复制和溶瘤潜力。在本研究中,适应了强毒力 NDV 在 HeLa 细胞中的复制,并通过观察凋亡的形态学、生化和核标志来评估其细胞毒性潜力。我们的结果表明,NDV 诱导 HeLa 细胞凋亡依赖于 TNF 相关凋亡诱导配体(TRAIL)和半胱天冬酶的激活。本研究中评估的不同凋亡决定因素表明,该毒株将来可能成为癌症治疗的有前途的候选者。