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Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells
Chen, Zan; Huang, Chen; Yang, Yan-ling; Ding, Yi; Ou-Yang, Han-qiang; Zhang, You-yi; Xu, Ming1
关键词Cepharanthine Anticancer Drug Human Osteosarcoma Cell Saos2 Cell Cycle Arrest Apoptosis Stat3 Nude Mice
刊名ACTA PHARMACOLOGICA SINICA
2012
DOI10.1038/aps.2011.164
33期:1页:101-108
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]NF-KAPPA-B ; BISCOCLAURINE ALKALOID CEPHARANTHINE ; OSTEOSARCOMA CELLS ; CARCINOMA-CELLS ; DOWN-REGULATION ; APOPTOSIS ; CANCER ; RESISTANCE ; TRANSCRIPTION ; INFLAMMATION
英文摘要

Aim: To investigate the molecular mechanisms underlying the antitumor activity of cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata.

Methods: Human osteosarcoma cell line SaOS2 was used. MTT assay, Hoechst 33342 nuclear staining, flow cytometry, Western blotting and nude mouse xenografts of SaOS2 cells were applied to examine the antitumor activity of CEP in vitro and in vivo. The expression levels of STAT3 and its downstream signaling molecules were measured with Western blotting and immunochemistry analysis. The activity of STAT3 was detected based on the phosphorylation level of STAT3, luciferase gene reporter assay and translocation of STAT3 to the nucleus.

Results: Treatment of SaOS2 cells with CEP (2.5-20 mu mol/L) inhibited the cell growth in a concentration-and time-dependent manner. CEP (10 mu mol/L) caused cell cycle arrest at G(1) phase and induced apoptosis of SaOS2 cells. CEP (10 and 15 mu mol/L) significantly decreased the expression of STAT3 in SaOS2 cells. Furthermore, CEP (5 and 10 mu mol/L) significantly inhibited the expression of target genes of STAT3, including the anti-apoptotic gene Bcl-xL and the cell cycle regulators c-Myc and cyclin D1. In nude mouse xenografts of SaOS2 cells, CEP (20 mg.kg(-1).d(-1), ip for 19 d) significantly reduced the volume and weight of the tumor.

Conclusion: Our findings suggest that inhibition of STAT3 signaling pathway is involved in the anti-tumor activity of CEP.

语种英语
WOS记录号WOS:000299213100015
项目编号81070196 ; 7082101 ; BMU20100012
资助机构National Natural Science Foundation ; Natural Science Foundation of Beijing ; Program for New Century Excellent Talents in University ; Beijing Talents Foundation
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57598
专题北京大学第三临床医学院
作者单位1.Peking Univ Third Hosp, Med Res Ctr, Inst Vasc Med, Beijing 100191, Peoples R China
2.Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Chen, Zan,Huang, Chen,Yang, Yan-ling,et al. Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells[J]. ACTA PHARMACOLOGICA SINICA,2012,33(1):101-108.
APA Chen, Zan.,Huang, Chen.,Yang, Yan-ling.,Ding, Yi.,Ou-Yang, Han-qiang.,...&Xu, Ming.(2012).Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells.ACTA PHARMACOLOGICA SINICA,33(1),101-108.
MLA Chen, Zan,et al."Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells".ACTA PHARMACOLOGICA SINICA 33.1(2012):101-108.
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