Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or Myc function and involves the induction of apoptosis
Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or Myc function and involves the induction of apoptosis
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DOI：
10.1128/jvi.75.7.3474-3479.2001
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发表时间：
2001-04-01
影响因子：
5.4
通讯作者：
Barber, GN
中科院分区：
文献类型：
--
作者：
Balachandran, S;Porosnicu, M;Barber, GN
我们最近发现水泡性口炎病毒（VSV）在体外和体内都表现出有效的溶瘤活性（S。Balachandran和G. N. Barber，IUBMB Life 50：135-138，2000），在该研究中，我们通过显示p53功能缺陷或用myc或活化ras转化的肿瘤也对病毒细胞溶解敏感，进一步证明了VSV抗肿瘤作用的体内功效。病毒溶瘤活性的机制涉及诱导多个半胱天冬酶依赖性凋亡途径，在没有任何显著细胞毒性T淋巴细胞应答的情况下有效，并且尽管PKR活性和eIF 2 α磷酸化正常，但仍发生。此外，VSV在免疫活性宿主中静脉内给药时可显著抑制肿瘤生长。我们的数据表明，VSV作为一种有效的溶瘤剂，对各种各样的恶性疾病，窝藏的遗传缺陷的多样性显着的承诺。
We have recently shown that vesicular stomatitis virus (VSV) exhibits potent oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. Barber, IUBMB Life 50:135-138, 2000), In this study, we further demonstrated, in vivo, the efficacy of VSV antitumor action by showing that tumors that are defective in p53 function or transformed with myc or activated ras are also susceptible to viral cytolysis. The mechanism of viral oncolytic activity involved the induction of multiple caspase-dependent apoptotic pathways was effective in the absence of any significant cytotoxic T-lymphocyte response, and occurred despite normal PKR activity and eIF2 alpha phosphorylation. In addition, VSV caused significant inhibition of tumor growth when administered intravenously in immunocompetent hosts. Our data indicate that VSV shows significant promise as an effective oncolytic agent against a wide variety of malignant diseases that harbor a diversity of genetic defects.