Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation.
Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation.
复制标题
DOI：
10.3390/ijms15034393
复制
发表时间：
2014-03-12
影响因子：
5.6
通讯作者：
Yang YP
中科院分区：
文献类型：
--
作者：
Ma HI;Hueng DY;Shui HA;Han JM;Wang CH;Lai YH;Cheng SY;Xiao X;Chen MT;Yang YP
多形性胶质母细胞瘤（GBM）是中枢神经系统恶性程度最高的肿瘤，临床预后差。在这项研究中，我们研究了抗癌蛋白，核心蛋白聚糖的治疗效果，通过将其递送到裸鼠脑中的异种移植瘤U87 MG胶质瘤通过腺相关病毒（AAV 2）基因递送系统。在体外从AAV载体表达核心蛋白聚糖通过诱导细胞分化抑制培养的U87 MG细胞生长。当与携带相同U87 MG肿瘤的对照未处理小鼠相比时，将AAV-核心蛋白聚糖载体颅内注射到体内携带胶质瘤的裸鼠显著抑制脑肿瘤生长并延长存活。对AAV介导的核心蛋白聚糖基因转移后U87 MG胶质瘤细胞中蛋白表达谱的蛋白质组学分析揭示了重要蛋白质的上调和下调。通过MALDI-TOF MS和数据库挖掘鉴定对照和AAV核心蛋白聚糖转导的细胞之间的差异表达蛋白。我们发现，参与细胞凋亡，转录，化疗抗性，有丝分裂和脂肪酸代谢的一些重要蛋白质已被改变作为核心蛋白聚糖过表达的结果。这些发现为核心蛋白聚糖的抗胶质母细胞瘤作用机制提供了有价值的见解。此外，AAV介导的核心蛋白聚糖基因递送作为脑肿瘤的潜在治疗方法值得进一步研究。
Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors.
登录
查看更多内容
影响因子：
30.8
作者：
KAPLITT, MG;LEONE, P;DURING, MJ
通讯作者：
DURING, MJ
影响因子：
5.1
作者：
Ma, HI;Lin, SZ;Xiao, X
通讯作者：
Xiao, X
影响因子：
7.5
作者：
Kwiatkowski, DJ
通讯作者：
Kwiatkowski, DJ
影响因子：
3.5
作者：
Grande, S.;Luciani, A. M.;Viti, V.
通讯作者：
Viti, V.
影响因子：
2.5
作者：
Katayama, Masafumi;Nakano, Hiroshi;Otsubo, Takehito
通讯作者：
Otsubo, Takehito