Dasatinib Suppresses Invasion And Induces Apoptosis In Nasopharyngeal Carcinoma

ObjectiveSFK (Src family kinase, SFK) belong to non-receptor tyrosine kniase. As the first discovered onprotein. Src plays a critical role in variety of cellular signal transduction pathways, regulating such diverse processes as cell division, motility, adhesion, invasion,survival and as so on. Also, elevated expression levels and activity of Src kinase have been observed in various human cancer cells and tumor tissues. Thus, Src kinase has been viewed as a significant target for cancer therapy and Src kinase inhibitors potentially provide new approaches toward cancer treatment. Related studies have shown that c-Src in nasopharyngeal carcinoma tissue expression was obviously higher than that of normal nasopharyngeal mucosa tissues, and c-Src expression in nasopharyngeal carcinoma tissue, respectively, and is closely related to the clinical stage and prognosis.This research is aimed to research the effects of dasatinib, a novel Src kinase inhibitor, on Nasopharyngeal Carcinoma cells in vitro.MethodsCell growth rate and 50% inhibitory concentration was calculated by MTT assay. Dasatinib-induced apoptotic cells were investigated by Annexin V/PI staining. Proteins from cell extracts were analyzed by Western blot. Cell motility was investigated by Transwell.Results(1) Dasatinib inhibited the proliferation of nasopharyngeal carcinoma cells in vitro.(2) Dasatinib inhibited phosphorylation of SRC in nasopharyngeal carcinoma.(3) Dasatinib inhibits Src downstream signaling.(4) Src inhibitionby Dasatinib leads to apoptosis in nasopharyngeal carcinoma.(5)Src inhibition by Dasatinib causes decreased migration.ConclusionOur study showed that Dasatinib significantly inhibited CNE2 proliferation and induced apoptosis in vitro. Its mechanisms were related to decreased level of tyrosine phosphorylation of Src. Phospho-AKT, phospho-MEK, phospho-ERK expression was significantly reduced when treated with dasatinib which means the downregulated RAS/RAF/MEK/ERK and PI3K/AKT pathway activity. Dasatinib significantly inhibited the motility of CNE2 as well as Phospho-FAK expression. Dasatinib exhibit antitumor effects of nasopharyngeal carcinoma by downregulating MAPK and PI3K/AKT pathways activity and FAK phosphorylation. This suggests that dasatinib would have therapeutic activity against NPC.