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学科主题基础医学
TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy
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
2013-10-01
DOI10.1007/s10495-013-0864-0
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
WOS记录号WOS:000324490000008
项目编号1R01NS072420-01
资助机构NIH/NINDS ; China Scholarship Council
引用统计
被引频次:25[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52840
专题北京大学基础医学院_病原生物学系
北京大学基础医学院
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
推荐引用方式
GB/T 7714
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.
APA Fan, Yihui.,Cheng, Jin.,Vasudevan, Sanjeev A..,Patel, Roma H..,Liang, Li.,...&Yang, Jianhua.(2013).TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy.APOPTOSIS,18(10),1224-1234.
MLA Fan, Yihui,et al."TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy".APOPTOSIS 18.10(2013):1224-1234.
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