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【答案】应助回帖
★ ★ ★ ★ ★
感谢参与，应助指数 +1
eveb: 金币+5, ★★★★★最佳答案, thanks 2014-11-13 12:32:24
jssxh: LS-EPI+1, 谢谢参与，请继续关注本版块 2014-11-13 14:59:25
https://apps.webofknowledge.com/ ... age=1&doc=1
Adenovirus-mediated transfer of siRNA against basic fibroblast growth factor mRNA enhances the sensitivity of glioblastoma cells to chemotherapy
作者:Feng, XQ (Feng, Xuequan)[ 1 ] ; Zhang, BA (Zhang, Biao)[ 2 ] ; Wang, JH (Wang, Jinhuan)[ 1,2 ] ; Xu, XN (Xu, Xinnv)[ 2 ] ; Lin, N (Lin, Na)[ 2 ] ; Liu, HS (Liu, Hongsheng)[ 2 ]
MEDICAL ONCOLOGY
卷: 28
期: 1
页: 24-30
DOI: 10.1007/s12032-010-9445-z
出版年: MAR 2011
查看期刊信息
摘要
Basic fibroblast growth factor (bFGF) is an important growth factor for glioma cell proliferation and invasion. BFGF is overexpressed in malignant gliomas and its level is associated with malignant grades and clinical outcome of patients with gliomas. Small interfering RNAs (siRNA) are synthetic forms of microRNA made of short double stranded RNA, and they effectively catalyze the degradation of their target mRNA. The use of siRNA has become a key method in the suppression of gene expression and the development of therapeutic agents. In this study, we used an adenovirus(Ad)-mediated transfer of siRNA against bFGF mRNA (Ad-bFGF-siRNA) to study the effect of down-regulating bFGF expression on the sensitivity of glioma cells to chemotherapeutics. An optimal siRNA sequence specific for bFGF mRNA was cloned into an adenoviral vector and transfected into three glioma cell lines: U251, A172, and LN229. Methyl thiazolyl tetrazolium (MTT) assays were used to examine changes in cell proliferation, and changes in bFGF mRNA and protein levels in U251 cells were detected using quantitative RT-PCR and Western blot, respectively. Apoptosis of U251 cells was detected using Hoechst staining and flow cytometry, with expression of apoptosis-related proteins evaluated by Western blot. Following the transfection of a bFGF-specific siRNA, mRNA and protein levels of bFGF decreased significantly. Lower rates of proliferation and increased levels of apoptosis also were associated with the Ad-bFGF-siRNA-transfected group compared to control group. Decreased expression of Bcl-2, Bcl-xL, Jak-1, and STAT-3 and increased expression of Bax also were detected in the Ad-bFGF-siRNA-transfected group. For cells treated with both Ad-bFGF-siRNA and chemotherapeutics, a significant reduction in cell survival was observed compared to treatment with Ad-bFGF-siRNA or chemotherapeutics alone. Overall, we found that targeting bFGF mRNA with a siRNA resulted in lower rates of proliferation, increased apoptosis, and enhanced sensitivity of glioma cells to chemotherapy drugs. This suggests that specific targeting of bFGF mRNA may provide a novel approach for the treatment of glioblastoma multiforme (GBM).
关键词
作者关键词:bFGF; Apoptosis; RNA interference; GBM
KeyWords Plus:C6 GLIOMA-CELLS; NUCLEAR ACCUMULATION; INHIBITION; EXPRESSION; APOPTOSIS; MECHANISMS; RECEPTOR
作者信息
通讯作者地址: Wang, JH (通讯作者)
Tianjin First Ctr Hosp, Dept Neurosurg, Fukang Rd 24, Tianjin 300192, Peoples R China.
地址:
[ 1 ] Tianjin First Ctr Hosp, Dept Neurosurg, Tianjin 300192, Peoples R China
[ 2 ] Tianjin First Ctr Hosp, Key Lab Crit Care Med, Minist Hlth, Tianjin 300192, Peoples R China
电子邮件地址:wangjinhuanfch@yahoo.com.cn
基金资助致谢
基金资助机构
授权号
National Natural Sciences Foundation of China
30672158
查看基金资助信息
出版商
HUMANA PRESS INC, 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
类别 / 分类
研究方向:Oncology
Web of Science 类别:Oncology
文献信息
文献类型:Article
语种:English
入藏号: WOS:000287756000004
PubMed ID: 20221717
ISSN: 1357-0560
期刊信息
Impact Factor (影响因子): Journal Citation Reports®
其他信息
IDS 号: 726VZ
Web of Science 核心合集中的 "引用的参考文献": 21
Web of Science 核心合集中的 "被引频次": 4 |
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