Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation
文献类型：期刊论文
| 作者 | Fan,Xiaoqing2; Yang,Haoran1,3 ; Zhao,Chenggang3; Hu,Lizhu3; Wang,Delong2; Wang,Ruiting2; Fang,Zhiyou1,3; Chen,Xueran1,3
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| 刊名 | Stem Cell Research & Therapy
 |
| 出版日期 | 2021-02-04 |
| 卷号 | 12 |
| 关键词 | Local anesthetics Glioblastoma stem cells Self-renewal ZDHHC15 GP130 STAT3 |
| DOI | 10.1186/s13287-021-02175-2 |
| 通讯作者 | Chen,Xueran(xueranchen@cmpt.ac.cn) |
| 英文摘要 | AbstractBackgroundA large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor?biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms.MethodsThe effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs.ResultsIn this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling.ConclusionsIn conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma. |
| 语种 | 英语 |
| 出版者 | BioMed Central |
| WOS记录号 | BMC:10.1186/S13287-021-02175-2 |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/125704]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Chen,Xueran |
| 作者单位 | 1.Chinese Academy of Sciences; Department of Medical Laboratory, Hefei Cancer Hospital 2.University of Science and Technology of China (USTC); Department of Anesthesiology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC 3.Hefei Institutes of Physical Science, Chinese Academy of Sciences; Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology |
| 推荐引用方式 GB/T 7714 | Fan,Xiaoqing,Yang,Haoran,Zhao,Chenggang,et al. Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation[J]. Stem Cell Research & Therapy,2021,12. |
| APA | Fan,Xiaoqing.,Yang,Haoran.,Zhao,Chenggang.,Hu,Lizhu.,Wang,Delong.,...&Chen,Xueran.(2021).Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation.Stem Cell Research & Therapy,12. |
| MLA | Fan,Xiaoqing,et al."Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation".Stem Cell Research & Therapy 12(2021). |
入库方式： OAI收割
来源：合肥物质科学研究院
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