The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model

Journal of Biomedical Science

Research

Mei-Jan Wang¹  Chin-Cheng Su²  Tsung-Lang Chiu³ 

[1] Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan;Tzu Chi College of Technology, Hualien, Taiwan, ROC;Department of surgery and Comprehensive Breast cancer center, Changhua Christian Hospital, Changhua, Taiwan;Tzu-Chi University, Hualien, Taiwan;Division of Neuro-Oncology, Neuro-Medical Scientific Center, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;

关键词: Microglial Cell;    Cystic Fibrosis Transmembrane Conductance Regulator;    Tumor Implantation;    Activate Microglia Cell;    BCNU Wafer;   

DOI  :  10.1186/1423-0127-19-45

 received in 2011-03-15, accepted in 2012-04-22,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMicroglial cells are the predominant immune cells in malignant brain tumors, but tumors may release some factors to reduce their defensive functions. Restoration of the anti-cancer function of microglia has been proposed as a treatment modality for glioblastoma. We examined the effect of intra-cranially administered recombinant adeno-associated virus encoding interleukin-12 (rAAV2/IL12) on transfection efficiency, local immune activity and survival in a rat model of glioblastoma multiforme.MethodsF344 rats were injected with rAAV2/IL12 and implanted with syngeneic RG2 cells (glioblastoma cell line). Intracerebral interleukin-12 and interferon-γ concentrations were determined by ELISA. Activation of microglia was determined by expressions of ED1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) which were evaluated by Western blotting and immunohistochemistry. The proliferation of cancer cells was evaluated with Ki67 immunohistochemistry and apoptosis of cancer cells with TUNEL.ResultsThe brains treated with rAAV2/IL-12 maintained high expression of interleukin-12 and interferon-γ for at least two months. In syngeneic tumor model, brains treated with rAAV2/IL12 exhibited more infiltration of activated microglia cells as examined by ED1 and TRAIL stains in the tumor. In addition, the volume of tumor was markedly smaller in AAV2/IL12-treated group and the survival time was significantly longer in this group too.ConclusionThe intra-cerebrally administered rAAV2/IL-12 efficiently induces long lasting expression of IL-12, the greater infiltration of activated microglia cells in the tumor associated improved immune reactions, resulting in the inhibited growth of implanted glioblastoma and the increased survival time of these rats.

【 授权许可】

Unknown   
© Chiu et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.