Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma.
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.
Yoshida
Jun
J
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan. jyoshida@med.nagoya-u.ac.jp
Mizuno
Masaaki
M
Nakahara
Norimoto
N
Colosi
Peter
P
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D016899:Interferon-beta