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

DOI: 10.1186/1479-5876-9-64

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Abstract:

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.Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in childhood, accounting for up to 50% of all soft tissue sarcomas [1]. While in adults, RMS represents about 15-20% of all soft tissue sarcomas [2]. There are two main histologically distinct subtypes of RMS: embryonal RMS (ERMS) and alveolar RMS (ARMS) [3]. ERMS is composed of spindle-shaped cells with a stromal rich appearance and occurs mainly in the head and neck region. It is the most frequently diagnosed variant with a generally good prognosis and presents early with an onset around the age of 2-5 years [3,4]. In contrast, ARMS consists of small, round, densely packed cells and occurs more often in the trunk and extremities. ARMS is primarily diagnosed in adolescents and is associated with a poor prognosis as patients often present with metastatic disease [5]. Chemotherapy is the most common therapeutic option for RMS. The regimens are typically based on variations of the well-established vincristine, actinomycin D and cyc

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