Abstract
Focal adhesion kinase (FAK) overexpression is related to the invasive and metastatic property in different kind of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatment, but its effect in human osteosarcoma has not yet well studied. In present study, we analyzed the anti-tumor efficacy of PF562271, a FAK inhibitor, against osteosarcoma in vitro and vivo. p-FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed the proliferation, colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and down-regulated the activity of AKT/mTOR pathway. Furthermore, PF562271 impaired tube formation ability of endothelial cells in vitro. Finally, oral administration of PF562271 in mice dramatically reduced tumor volume, weight and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma.
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