Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274.
Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274.
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DOI：
10.1186/1479-5876-9-64
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发表时间：
2011-05-16
影响因子：
7.4
通讯作者：
Ding SJ
中科院分区：
文献类型：
--
作者：
Hou J;Dong J;Sun L;Geng L;Wang J;Zheng J;Li Y;Bridge J;Hinrichs SH;Ding SJ
c-Met是一种受体酪氨酸激酶（RTK），在多种癌症中过表达，并参与细胞生长、侵袭、转移和血管生成。在这项研究中，我们研究了c-Met在横纹肌肉瘤（RMS）中的作用，使用其小分子抑制剂SU 11274，这已被假设为RMS的潜在治疗靶点。分别采用磷酸化RTK芯片和免疫组织化学方法检测磷酸化c-Met在RMS细胞系（RD、CW 9019和RH 30）和肿瘤组织中的表达水平。研究了SU 11274对RMS细胞的细胞内信号传导、细胞增殖、细胞周期和细胞迁移的抑制作用。在2个肺泡RMS细胞系（CW 9019和RH 30）和24个RMS组织样本中的14个中检测到高水平的磷酸化c-Met，而在胚胎RMS细胞系（RD）中观察到相对低水平的磷酸化c-Met。小分子SU 11274可显著降低c-Met的磷酸化水平，抑制CW 9019和RH 30细胞增殖，使细胞周期阻滞于G1期，并阻断细胞迁移。这些结果可能支持c-Met在RMS的发生和发展中的作用。c-Met抑制剂SU 11274可作为RMS尤其是肺泡型RMS的有效靶向治疗剂。
c-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. The 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. A 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. These 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.
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影响因子：
3.4
作者：
CALLENDER, TA;WEBER, RS;ELNAGGAR, A
通讯作者：
ELNAGGAR, A
影响因子：
6.2
作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
Meyer, William H.
DOI：
10.1111/j.1525-1438.2007.01135.x
发表时间：
2008-09-01
影响因子：
4.8
作者：
Koon, E. C.;Ma, P. C.;Mok, S. C.
通讯作者：
Mok, S. C.