Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis

doi:10.2147/CMAR.S240268

	Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis
	Wang, Qiong 1,2,3; Wang, Zeng 1,2,3; Hou, Guilan 1,2,3; Huang, Ping 1,2,3
刊名	CANCER MANAGEMENT AND RESEARCH
	2020
卷号	12
关键词	glioma TSN miR-608 Notch1 and Notch2 tumor growth metastasis
ISSN号	1179-1322
DOI	10.2147/CMAR.S240268
通讯作者	Huang, Ping(PingHuangfjk@163.com)
英文摘要	Background: Glioma is one the most common and aggressive primary tumors of adult central nervous system worldwide, which tends to develop dysplasia and metastasis. Recently, toosendanin (TSN) has shown pharmacological effects in several cancers. However, little is known about the underlying mechanism of the effect of TSN on glioma and its relationship between miRNA in glioma. Methods: Cell proliferation, cell cycle, cell apoptosis and cell migration were analyzed by CCK-8 cell viability, flow cytometry, wound scratch healing, transwell and Western blotting assays, respectively, in vitro. The regulation relationships between TSN and miR-608 or between miR-608 and Notch1 (Notch2) were examined using qRT-PCR, dual-luciferase and Western blotting assays. The functional effects of TSN through regulating miR-608 and Notch1 (Notch2) were further examined using a xenograft tumor mouse model in vivo. Results: After TSN concentration was increased from 50 nM, 100 nM to 150 nM, cell proliferation and cell cycle were gradually reduced, and the cell apoptosis rate was increased in U-138MG or U-251MG cells. Wound-healing and transwell assays results showed that cell migration was significantly inhibited in TSN treatment cells (TSN treatment, 50 nM) compared to control cells. Mechanistic studies revealed that TSN up-regulated the expression of microRNA-608 (miR-608), while down-regulated the expression of miR-608's target, Notch1 and Notch2. Over-expression of Notch1 and Notch2 partly attenuated TSN-induced tumor suppressive function. Moreover, in vivo experiments revealed that TSN treatment led to a significant inhibition of tumor growth, suggesting that it might be a promising drug for the treatment of glioma. Conclusion: In the present study, a novel established functional manner of TSN/miR-608/Notch1 (Notch2) axis was systematically indicated, which might provide prospective intervention ways for glioma therapy.
资助项目	Zhejiang Provincial National Science Foundation of China[YQ20H280002] ; Zhejiang Provincial National Science Foundation of China[Q18H290004]
WOS关键词	PANCREATIC-CANCER ; STEM-CELLS ; MIGRATION ; INVASION ; MICRORNA ; GROWTH ; PROLIFERATION ; TUMORIGENESIS ; EXPRESSION ; NOTCH
WOS研究方向	Oncology
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000531772700001
资助机构	Zhejiang Provincial National Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103325]
专题	中国科学院合肥物质科学研究院
通讯作者	Huang, Ping
作者单位	1.Zhejiang Canc Hosp, Dept Pharm, 1 Guangji East Rd, Hangzhou 310022, Zhejiang, Peoples R China 2.Chinese Acad Sci, Dept Pharm, Inst Canc & Basic Med Sci, Hangzhou 310022, Zhejiang, Peoples R China 3.Univ Chinese Acad Sci, Dept Pharm, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Wang, Qiong,Wang, Zeng,Hou, Guilan,et al. Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis[J]. CANCER MANAGEMENT AND RESEARCH,2020,12.
APA	Wang, Qiong,Wang, Zeng,Hou, Guilan,&Huang, Ping.(2020).Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis.CANCER MANAGEMENT AND RESEARCH,12.
MLA	Wang, Qiong,et al."Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis".CANCER MANAGEMENT AND RESEARCH 12(2020).