GSK-3 inhibitor CHIR99021 enriches glioma stem-like cells | |
Yang, Yang3,4,5; Wang, Qin-Qin5; Bozinov, Oliver3,4; Xu, Ru-Xiang5; Sun, Yi-Lin1,5; Wang, Shan-Shan2 | |
刊名 | ONCOLOGY REPORTS |
2020-05-01 | |
卷号 | 43期号:5页码:1479-1490 |
关键词 | glioma stem-like cells CHIR99021 STAT3 PI3K AKT signaling pathway temozolomide |
ISSN号 | 1021-335X |
DOI | 10.3892/or.2020.7525 |
产权排序 | 5 |
文献子类 | Article |
英文摘要 | 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. |
资助项目 | Beijing Municipal Science & Technology Commission[Z17110000101] ; China Scholarship Council[201709110116] |
WOS关键词 | GENE-EXPRESSION ; GLIOBLASTOMA ; RESISTANCE ; DIFFERENTIATION ; TEMOZOLOMIDE |
WOS研究方向 | Oncology |
语种 | 英语 |
出版者 | SPANDIDOS PUBL LTD |
WOS记录号 | WOS:000526743200011 |
资助机构 | Beijing Municipal Science & Technology Commission ; China Scholarship Council |
内容类型 | 期刊论文 |
源URL | [http://ir.psych.ac.cn/handle/311026/31570] |
专题 | 心理研究所_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.Tiantan Hosp, Beijing Inst Neurosurg, Ultramicropathol Lab, Beijing 100050, Peoples R China 2.Chinese Acad Sci, Inst Psychol, 16 Lincui Rd, Beijing 100101, Peoples R China 3.Univ Zurich, Univ Zurich Hosp, Dept Neurosurg, Frauenklin Str 10, CH-8091 Zurich, Switzerland 4.Canton Hosp St Gallen, Dept Neurosurg, CH-9007 St Gallen, Switzerland 5.PLA Army Gen Hosp, Neurosurg Inst, Seventh Med Ctr, Beijing 100700, Peoples R China |
推荐引用方式 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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