Dasatinib suppresses invasion and induces apoptosis in nasopharyngeal carcinoma.
Dasatinib, an orally available tyrosine kinas inhibitor (TKI), potently inhibits SRC which was found to activate RTKs that induce trastuzumab de novo and acquired resistance. To evaluate the potential of Dasatinib in the treatment of Nasopharyngeal Carcinoma, we used a variety of assays to measure its effects on cell proliferation, apoptosis, and migration. This work aimed to test the antitumor effects of the inhibitor in vitro to determine whether in vivo analyses were warranted. Cell 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. Our study showed that Dasatinib significantly inhibited CNE2 proliferation and induced apoptosis in vitro. 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.
Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, PR. China.
Yu-Jie
YJ
Li
Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, PR. China.
Yi-Fu
YF
He
Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, PR. China.
Xing-Hua
XH
Han
Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, PR. China.
Bing
B
Hu
D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
D019869:Phosphatidylinositol 3-Kinases; D000069439:Dasatinib
CNE2; FAK; Nasopharyngeal carcinoma; PI3K/AKT; RAS/RAF/MEK/ERK; dasatinib