Yoshida Jun, Mizuno Masaaki, Nakahara Norimoto, Colosi Peter
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Jpn J Cancer Res. 2002 Feb;93(2):223-8. doi: 10.1111/j.1349-7006.2002.tb01262.x.
We constructed an adeno-associated virus (AAV) vector containing the human interferon-beta (HuIFN-b ) gene (AAV-IFN-beta) and investigated its antitumor effect against human glioma cells (U251-SP) inoculated into the brain of nude mice. Prior to this, we examined human glioma cells transduced with AAV-IFN-beta using video-enhanced contrast differential interference contrast (VEC-DIC) microscopy. Infection of AAV-IFN-beta induced apoptosis and secondary necrosis in human glioma cells. In in vivo experiments, we confirmed production of HuIFN-beta and induction of heat-shock protein (HSP) in glioma cells transduced with AAV-IFN-beta. Growth of the experimental gliomas was completely inhibited by six injections of AAV-IFN-beta, starting 7 days after transplantation of glioma cells. In addition, the survival of mice treated with AAV-IFN-beta was remarkably prolonged. These results indicate that AAV-IFN-beta induces apoptosis of glioma cells and has a strong antitumor effect in this experimental glioma model.
我们构建了一种携带人干扰素-β（HuIFN-β）基因的腺相关病毒（AAV）载体（AAV-IFN-β），并研究了其对接种于裸鼠脑内的人胶质瘤细胞（U251-SP）的抗肿瘤作用。在此之前，我们使用视频增强对比微分干涉对比（VEC-DIC）显微镜检查了用AAV-IFN-β转导的人胶质瘤细胞。AAV-IFN-β感染诱导人胶质瘤细胞凋亡和继发性坏死。在体内实验中，我们证实了用AAV-IFN-β转导的胶质瘤细胞中HuIFN-β的产生和热休克蛋白（HSP）的诱导。从胶质瘤细胞移植后7天开始，六次注射AAV-IFN-β可完全抑制实验性胶质瘤的生长。此外，用AAV-IFN-β治疗的小鼠存活时间显著延长。这些结果表明，AAV-IFN-β诱导胶质瘤细胞凋亡，并在该实验性胶质瘤模型中具有强大的抗肿瘤作用。
