Background: The purpose of our study was to investigate the anticancer effect of sorafenib on mucoepidermoid carcinoma (MEC) and find its new molecular mechanism.
Methods: The apoptotic effects of sorafenib were performed using MTS assay, diamidino-phenylindole (DAPI) staining, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), siRNA, and xenograft.
Results: Sorafenib had apoptotic effects on MC-3 and YD15 cells and decreased myeloid cell leukemia-1 (Mcl-1) through proteasome-dependent protein degradation and the inhibition of protein synthesis. Sorafenib significantly affected truncated bid (t-Bid) and siMcl-1 resulting in the upregulation of t-Bid to induce apoptosis. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was also blocked by sorafenib and a potent STAT3 inhibitor, cryptotanshinone clearly induced poly ADP-ribose polymerase (PARP) cleavage by inhibiting Mcl-1 and increasing t-Bid. Finally, administration of sorafenib significantly suppressed tumor growth and induced apoptosis in tumor xenograft model in association with downregulation of Mcl-1 without any side effects.
Conclusion: Taken together, these findings suggest that sorafenib can be a good anticancer drug candidate for the treatment of MEC.
Keywords: apoptosis; mucoepidermoid carcinoma; myeloid cell leukemia-1 (Mcl-1); signal transducer and activator of transcription 3 (STAT3); sorafenib.
© 2014 Wiley Periodicals, Inc.