Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells

doi:10.1016/j.canlet.2012.09.019

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells
	Yang, Jie 1,2; Cai, Xueting 1; Lu, Wuguang 1; Hu, Chunping 1; Xu, Xiaojun 2; Yu, Qiang3 ; Cao, Peng 1,2
刊名	CANCER LETTERS
	2013-01-28
卷号	328 期号:2 页码:243-251
关键词	Evodiamine STAT3 SHP-1 HCC Inhibitor
ISSN号	0304-3835
DOI	10.1016/j.canlet.2012.09.019
文献子类	Article
英文摘要	The activation of signal transducer and activator of transcription signaling 3 (STAT3) has been linked with the survival, proliferation, angiogenesis and immunosuppression of hepatocellular carcinoma cells (HCCs). Agents that can suppress STAT3 activation have potential to be cancer therapeutics. In this study, we investigated the inhibitory effect of evodiamine on STAT3 pathway in vitro and the anti-tumor effect of evodiamine in vivo in HCC. We found that evodiamine suppressed both constitutive and interleukin-6 (IL-6)-induced activation of STAT3 tyrosine 705 (Tyr(705)) effectively. The phosphorylation of Janus-activated kinase 2 (JAK2), Src and extracellular regulated protein kinases 1/2 (ERK1/2) were also suppressed by evodiamine. Interestingly, treatment of cells with sodium pervanadate abrogated the inhibition of evodiamine on IL-6-induced STAT3 (Tyr(705)) activation indicating the involvement of protein tyrosine phosphatases. Indeed, further studies demonstrated that evodiamine induced the expression of phosphatase shatterproof 1 (SHP-1). Moreover, inhibition of SHP-1 gene by small interference RNA abolished the ability of evodiamine to inhibit IL-6-induced STAT3 (Tyr(705)) activation. Evodiamine also suppressed STAT3 DNA binding activity and down-regulated the expression of STAT3-mediated genes leading to the suppression of proliferation, induction of cell apoptosis and cell cycle arrest. In vivo, evodiamine significantly inhibited tumor growth in a subcutaneous xenograft model with HepG2 cells. In summary, evodiamine blocked STAT3 signaling pathway by inducing SHP-1 and exhibited anticancer effect in vitro and in vivo. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81202967] ; National Natural Science Foundation of China[81274150] ; National Natural Science Foundation of China[30873410] ; National Natural Science Foundation of China[81073101] ; National Natural Science Foundation of China[31129004] ; National Natural Science Foundation of China[91129701] ; Open Project Program of State Key Laboratory of Natural Medicine, China Pharmaceutical University[SKLNMKF201203] ; Jiangsu Provinces Outstanding Leader Program of Traditional Chinese Medicine[00000000] ; National Science & Technology Key Project Grant[2012CB910704]
WOS关键词	NF-KAPPA-B ; DEPENDENT APOPTOSIS ; GENE-EXPRESSION ; IN-VIVO ; ACTIVATION ; GROWTH ; ANGIOGENESIS ; PHOSPHORYLATION ; INTERLEUKIN-6 ; METASTASIS
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000313138000008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277760]
专题	药理学第一研究室
通讯作者	Cao, Peng
作者单位	1.Jiangsu Prov Inst Tradit Chinese, Lab Cellular & Mol Biol, Nanjing 210028, Jiangsu, Peoples R China; 2.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yang, Jie,Cai, Xueting,Lu, Wuguang,et al. Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells[J]. CANCER LETTERS,2013,328(2):243-251.
APA	Yang, Jie.,Cai, Xueting.,Lu, Wuguang.,Hu, Chunping.,Xu, Xiaojun.,...&Cao, Peng.(2013).Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells.CANCER LETTERS,328(2),243-251.
MLA	Yang, Jie,et al."Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells".CANCER LETTERS 328.2(2013):243-251.