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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
First AuthorYang, Yang
Correspondent Emailoliver.bozinov@usz.ch
2020-05-01
Source PublicationONCOLOGY REPORTS
ISSN1021-335X
SubtypeArticle
Volume43Issue:5Pages:1479-1490
QuartileQ2
Contribution Rank5
Abstract

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.

Keywordglioma stem-like cells CHIR99021 STAT3 PI3K AKT signaling pathway temozolomide
DOI10.3892/or.2020.7525
Indexed BySCI
Language英语
Funding OrganizationBeijing Municipal Science & Technology Commission ; China Scholarship Council
Funding ProjectBeijing Municipal Science & Technology Commission[Z17110000101] ; China Scholarship Council[201709110116]
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000526743200011
PublisherSPANDIDOS PUBL LTD
WOS KeywordGENE-EXPRESSION ; GLIOBLASTOMA ; RESISTANCE ; DIFFERENTIATION ; TEMOZOLOMIDE
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/31571
Collection健康与遗传心理学研究室
Corresponding AuthorBozinov, Oliver; Wang, Shan-Shan
Affiliation1.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
Recommended Citation
GB/T 7714
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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