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GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells
Yang, Yang1,2,3; Wang, Qin-Qin3; Bozinov, Oliver1,2; Xu, Ru-Xiang3; Sun, Yi-Lin3,4; Wang, Shan-Shan5
第一作者Yang, Yang
通讯作者邮箱oliver.bozinov@usz.ch
心理所单位排序5
摘要

Glioblastoma (GBM) is the most prevalent and lethal primary intrinsic brain cancer. The disease is essentially incurable, with glioblastomas characterized by resistance to both chemotherapy and radiotherapy, as well as by rapid tumor progression, all of which are mainly ascribed to glioma stem-like cells (GSLCs). In the present study, an improved model that is more similar to clinical GBM was constructed. Twenty clinical glioma samples were collected to obtain primary low-grade tumor cells. The cells were either maintained in serum-free medium as primary glioma-based cells (PGBCs) or cultured in the same medium with CHIR99021 as GSLCs. Then, the molecular and ultrastructural differences between the two cell groups were determined. Furthermore, the proliferation and migration of the GSLCs were examined and the potential mechanisms were investigated. Finally, temozolomide resistance in vitro and in the mouse model was assessed to study the properties of the induced GSLCs. The primary low-grade tumor cells extracted from surgical samples were enriched with GSLC properties, with high expression levels of CD133 and Nestin in 100 nM CHIR99021. The GSLCs exhibited high proliferation and migration. Furthermore, the expression of the PI3K/AKT signaling pathway and that of related genes and proteins were significantly enhanced by CHIR99021. The animal study also revealed high levels of STAT3, mTOR, NF-kappa B, and VEGF in the GSLC-transplanted mice. CHIR99021 could stably enhance GSLC properties in patient-derived glioma samples. It may provide a useful model for further study, helping to understand the pathogenesis of therapeutic resistance and to screen drug candidates.

关键词glioma stem-like cells CHIR99021 STAT3 PI3K AKT signaling pathway temozolomide
2020-05-01
语种英语
DOI10.3892/or.2020.7525
发表期刊ONCOLOGY REPORTS
ISSN1021-335X
卷号43期号:5页码:1479-1490
期刊论文类型Article
收录类别SCI
资助项目Beijing Municipal Science & Technology Commission[Z17110000101] ; China Scholarship Council[201709110116]
出版者SPANDIDOS PUBL LTD
WOS关键词GENE-EXPRESSION ; GLIOBLASTOMA ; RESISTANCE ; DIFFERENTIATION ; TEMOZOLOMIDE
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000526743200011
Q分类Q2
资助机构Beijing Municipal Science & Technology Commission ; China Scholarship Council
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/31571
专题健康与遗传心理学研究室
通讯作者Bozinov, Oliver; Wang, Shan-Shan
作者单位1.Univ Zurich, Univ Zurich Hosp, Dept Neurosurg, Frauenklin Str 10, CH-8091 Zurich, Switzerland
2.Canton Hosp St Gallen, Dept Neurosurg, CH-9007 St Gallen, Switzerland
3.PLA Army Gen Hosp, Neurosurg Inst, Seventh Med Ctr, Beijing 100700, Peoples R China
4.Tiantan Hosp, Beijing Inst Neurosurg, Ultramicropathol Lab, Beijing 100050, Peoples R China
5.Chinese Acad Sci, Inst Psychol, 16 Lincui Rd, Beijing 100101, Peoples R China
通讯作者单位中国科学院心理研究所
推荐引用方式
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Yang, Yang,Wang, Qin-Qin,Bozinov, Oliver,et al. GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells[J]. ONCOLOGY REPORTS,2020,43(5):1479-1490.
APA Yang, Yang,Wang, Qin-Qin,Bozinov, Oliver,Xu, Ru-Xiang,Sun, Yi-Lin,&Wang, Shan-Shan.(2020).GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells.ONCOLOGY REPORTS,43(5),1479-1490.
MLA Yang, Yang,et al."GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells".ONCOLOGY REPORTS 43.5(2020):1479-1490.
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