学科主题临床医学
Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway
Peng, Chang-Liang; Guo, Wei; Ji, Tao; Ren, Tingting; Yang, Yi; Li, Da-Sen; Qu, Hua-Yi; Li, Xiao; Tang, Shun; Yan, Tai-Qiang; Tang, Xiao-Dong
关键词synovial sarcoma sorafenib MAPK apoptosis SW982 HS-SY-II cell cycle
刊名CANCER BIOLOGY & THERAPY
2009-09-15
8期:18页:1729-1736
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]BCL-2 PROTEIN FAMILY ; CYCLIN D1 EXPRESSION ; SOFT-TISSUE TUMORS ; FACTOR RECEPTOR ; FUSION TYPE ; CANCER ; GENE ; KINASES ; SYT ; SSX
英文摘要

Synovial sarcoma is a soft tissue sarcoma with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. Mitogen-activated protein kinase (MAPK) cascades have been shown to play important roles in synovial sarcoma survival. Sorafenib (Nexavar, BAY 43-9006), a potent recombinant activated factor (RAF) inhibitor, inhibits the MAPK signaling pathway both in vitro and in vivo. In this study, we examined the inhibitory proliferation effects of sorafenib in synovial sarcoma growth and evaluated whether sorafenib modulates MAPK and tumor apoptosis cascades in human synovial sarcoma cell lines SW982 and HS-SY-II. Our results indicated that sorafenib effectively inhibited cellular proliferation and induces apoptosis of these two cells. Sorafenib inhibited the phosphorylation of MEK and ERK, downregulated cyclin D1 and Rb levels, caused G(1) arrest and S phase decrease, and induced apoptosis as confirmed by flow cytometry and the TUNEL assay. Furthermore, Bcl-xl and Mcl-1 levels significantly decreased, whereas expression levels of the proteins bcl-2 and bax were unchanged in response to sorafenib treatment in SW982 and HS-SY-II cells. In conclusion, our findings demonstrate that sorafenib is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that sorafenib may be a new therapeutic option for patients with synovial sarcoma.

语种英语
WOS记录号WOS:000271424700009
项目编号30571869 ; 2005-1009
资助机构National Natural Science Foundation of China ; Capital Medical Development and Research Foundation
引用统计
被引频次:36[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/400002259/65668
专题北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学第二临床医学院_骨肿瘤科
作者单位Peking Univ, Musculoskeletal Tumor Ctr, Peoples Hosp, Beijing 100044, Peoples R China
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Peng, Chang-Liang,Guo, Wei,Ji, Tao,et al. Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway[J]. CANCER BIOLOGY & THERAPY,2009,8(18):1729-1736.
APA Peng, Chang-Liang.,Guo, Wei.,Ji, Tao.,Ren, Tingting.,Yang, Yi.,...&Tang, Xiao-Dong.(2009).Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway.CANCER BIOLOGY & THERAPY,8(18),1729-1736.
MLA Peng, Chang-Liang,et al."Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway".CANCER BIOLOGY & THERAPY 8.18(2009):1729-1736.
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