XJIPC OpenIR  > 省部共建新疆特有药用资源利用重点实验室
Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis
Chen, ZH (Chen, Zhenghu); Wang, L (Wang, Long); Yao, DY (Yao, Dayong); Yang, TS (Yang, Tianshu); Cao, WM (Cao, Wen-Ming); Dou, J (Dou, Jun); Pang, JC (Pang, Jonathan C.); Guan, S (Guan, Shan); Zhang, HY (Zhang, Huiyuan); Yu, Y (Yu, Yang); Zhao, YL (Zhao, Yanling); Wang, YF (Wang, Yongfeng); Xu, X (Xu, Xin); Shi, Y (Shi, Yan); Patel, R (Patel, Roma); Zhang, H (Zhang, Hong); Vasudevan, SA (Vasudevan, Sanjeev A.); Liu, SF (Liu, Shangfeng); Yang, JH (Yang, Jianhua); Nuchtern, JG (Nuchtern, Jed G.)
2016
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume6Issue:12Pages:1-12
Abstract

Neuroblastoma (NB) is the most common extracranial tumor in children. Unlike in most adult tumors, tumor suppressor protein 53 (p53) mutations occur with a relatively low frequency in NB and the downstream function of p53 is intact in NB cell lines. Wip1 is a negative regulator of p53 and hindrance of Wip1 activity by novel inhibitor GSK2830371 is a potential strategy to activate p53's tumor suppressing function in NB. Yet, the in vivo efficacy and the possible mechanisms of GSK2830371 in NB have not yet been elucidated. Here we report that novel Wip1 inhibitor GSK2830371 induced Chk2/p53-mediated apoptosis in NB cells in a p53-dependent manner. In addition, GSK2830371 suppressed the colony-formation potential of p53 wild-type NB cell lines. Furthermore, GSK2830371 enhanced doxorubicin-(Dox) and etoposide-(VP-16) induced cytotoxicity in a subset of NB cell lines, including the chemoresistant LA-N-6 cell line. More importantly, GSK2830371 significantly inhibited tumor growth in an orthotopic xenograft NB mouse model by inducing Chk2/p53-mediated apoptosis in vivo. Taken together, this study suggests that GSK2830371 induces Chk2/p53-mediated apoptosis both in vitro and in vivo in a p53 dependent manner.

DOI10.1038/srep38011
Indexed BySCI
WOS IDWOS:000389884900001
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/4712
Collection省部共建新疆特有药用资源利用重点实验室
Affiliation1.Tongji Univ, Shanghai Peoples Hosp 10, Dept Ophthalmol, Sch Med, Shanghai 200072, Peoples R China
2.Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
3.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
4.Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Dept Acupuncture, Harbin 150040, Heilongjiang, Peoples R China
5.Harbin Med Univ, Affiliated Hosp 1, Dept Urol, Harbin 150001, Heilongjiang, Peoples R China
6.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou 310022, Zhejiang, Peoples R China
7.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi 830011, Xinjiang, Peoples R China
8.Baylor Coll Med, Div Pediat Surg, Michael DeBakey Dept Pediat Surg, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
9.Fudan Univ, Huashan Hosp, Dept Stomatol, Shanghai 200040, Peoples R China
Recommended Citation
GB/T 7714
Chen, ZH ,Wang, L ,Yao, DY ,et al. Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis[J]. SCIENTIFIC REPORTS,2016,6(12):1-12.
APA Chen, ZH .,Wang, L .,Yao, DY .,Yang, TS .,Cao, WM .,...&Nuchtern, JG .(2016).Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis.SCIENTIFIC REPORTS,6(12),1-12.
MLA Chen, ZH ,et al."Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis".SCIENTIFIC REPORTS 6.12(2016):1-12.
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