Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274

Journal of Translational Medicine

Research

Yan Li¹  Steven H Hinrichs²  Shi-Jian Ding²  Julia Bridge²  Jinxuan Hou³  Lijun Sun⁴  Jialin Zheng⁴  Jing Wang⁵  Liying Geng⁵  Jixin Dong⁵ 

[1] Department of Oncology, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China;Department of Pathology and Microbiology, University of Nebraska Medical Center, 68105, Omaha, USA;Department of Pathology and Microbiology, University of Nebraska Medical Center, 68105, Omaha, USA;Department of Oncology, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China;Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 68105, Omaha, USA;Eppley Cancer Institute, University of Nebraska Medical Center, 68105, Omaha, USA;

关键词: Hepatocyte Growth Factor;    SU11274;    RH30 Cell;    Inhibitor SU11274;    Hepatocyte Growth Factor Treatment;   

DOI  :  10.1186/1479-5876-9-64

 received in 2010-12-06, accepted in 2011-05-16,  发布年份 2011

来源: Springer

【 摘 要 】

Backgroundc-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.MethodsThe expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle and cell migration.ResultsA high level of phosphorylated c-Met was detected in 2 alveolar RMS cell lines (CW9019 and RH30) and 14 out of 24 RMS tissue samples, whereas relatively low levels of phospho-c-Met were observed in the embryonic RMS cell line (RD). The small molecule SU11274 could significantly reduce the phosphorylation of c-Met, resulting in inhibition of cell proliferation, G1 phase arrest of cell cycle and blocking of cell migration in CW9019 and RH30 cell lines.ConclusionThese results might support the role of c-Met in the development and progression of RMS. Furthermore, the inhibitor of c-Met, SU11274, could be an effective targeting therapy reagent for RMS, especially alveolar RMS.

【 授权许可】

Unknown   
© Hou et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.