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学科主题: 基础医学
题名:
TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy
作者: Fan, Yihui1,2; Cheng, Jin1,2,3; Vasudevan, Sanjeev A.2,4; Patel, Roma H.2,4; Liang, Li5; Xu, Xin1,2; Zhao, Yanling1,2; Jia, Wei5; Lu, Fengmin3; Zhang, Hong5; Nuchtern, Jed G.2,4; Kim, Eugene S.2,4; Yang, Jianhua1,2
关键词: Neuroblastoma ; TAK1 inhibitor ; 5Z-7-oxozeaenol ; Chemotherapy
刊名: APOPTOSIS
发表日期: 2013-10-01
DOI: 10.1007/s10495-013-0864-0
卷: 18, 期:10, 页:1224-1234
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: NF-KAPPA-B ; DNA-DAMAGE RESPONSE ; SIGNALING PATHWAYS ; GENOTOXIC STRESS ; ACTIVATION ; KINASE ; TARGET ; CANCER ; INFLAMMATION ; UBIQUITIN
英文摘要:

Treatment failure in high risk neuroblastoma is largely due to development of chemoresistance. NF-kappa B activation is one of the resistance mechanisms for cancer cells to escape from chemotherapy-induced cell-death. TAK1 is an essential component in genotoxic stresses-induced NF-kappa B activation; however, the role of TAK1 in the development of chemoresistance in neuroblastoma remains unknown. Using a panel of neuroblastoma cell lines, we found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) on neuroblastoma cell lines. TAK1 inhibition also enhanced the inhibitory effect of Dox and VP-16 on anchorage-independent growth. Treatment of neuroblastoma cells with 5Z-7-oxozeaenol blocked Dox- and VP16-induced NF-kappa B activation and enhanced Dox- and VP16-induced apoptosis. Moreover, 5Z-7-oxozeaenol was able to overcome the established chemoresistance in LA-N-6 neuroblastoma cells. Using an orthotopic neuroblastoma mouse model, we found that 5Z-7-oxozeaenol significantly enhanced chemotherapeutic efficacy in vivo. Together, our results provide a proof-of-concept that TAK1 inhibition significantly increases the sensitivity of neuroblastoma cells to chemotherapy-induced cell-death and can serve as an effective adjunct to current chemotherapeutic regimens for high risk diseases.

语种: 英语
所属项目编号: 1R01NS072420-01
项目资助者: NIH/NINDS ; China Scholarship Council
WOS记录号: WOS:000324490000008
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52840
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Houston, TX 77030 USA
2.Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
3.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China
4.Baylor Coll Med, Div Pediat Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA
5.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

Recommended Citation:
Fan, Yihui,Cheng, Jin,Vasudevan, Sanjeev A.,et al. TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy[J]. APOPTOSIS,2013,18(10):1224-1234.
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