Abstract
Background
The multi‐kinase inhibitor sorafenib displays antitumoral effects in head and neck squamous cell carcinoma (HNSCC); however, the targeted kinases are unknown. Here we aimed to identify those kinases to determine the mechanism of sorafenib‐mediated effects and establish candidate biomarkers for patient stratification.
Methods
The effects of sorafenib and MET inhibitors crizotinib and SU11274 were analyzed using a slide‐based antibody array, Western blotting, proliferation, and survival assays. X‐rays were used for irradiations.
Results
Sorafenib inhibited auto‐phosphorylation of epidermal growth factor receptor and MET, which has not been described previously. MET expression in HNSCC cells was not always associated with activity/phosphorylation. Furthermore, sorafenib‐dependent cell kill and radiosensitization was not associated with MET level. Although MET inhibitors blocked proliferation, they caused only mild cytotoxicity and no radiosensitization.
Conclusion
We identified MET as a new potential target of sorafenib. However, MET inhibition is not the cause for sorafenib‐mediated cytotoxicity or radiosensitization.
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