Targeting the JAK1 /STAT3 Signaling Pathway: Entinostat as a Promising Treatment for Nasopharyngeal Carcinoma

Background In various cancer types, entinostat (MS275) inhibits histone deacetylase (HDAC) selectively and exhibits anti-tumor activity. Our study aims to investigate the effects of MS-275 on nasopharyngeal carcinoma (NPC) cells. Methods CNE-2 and HONE-1 cell lines were used to carry out the experiments. CCK-8, clone formation assay, DAPI staining, mitochondrial membrane potential (MMP), flow cytometry, wound healing, transwell assay and western blot analyses were used to assess MS-275's effects on NPC cells. Results MS-275 inhibited NPC cells from proliferating in a dose-and time-dependent manner. The G2 phase DNA proportion obviously increased with the MS-275 concentration increase (P < 0.05). MS-275 can induce apoptosis of nasopharyngeal carcinoma cells and then cause the decrease of mitochondrial membrane potential. In addition to inhibiting NPC invasion, MS-275 can also suppress cell migration. With increasing drug concentration, the phosphorylation of JAK1 and STAT3 was significantly prevented, while their expression remained unchanged. This is consistent with the immunofluorescence and confocal laser-scanning microscopy result. The metastasis-relevant MMP-2, Snail, anti-apoptotic protein Bcl-xL and Bcl-2 were all downregulated, while the metastasis-relevant E-cadherin, pro-apoptotic protein Bax and cyclin dependent kinase inhibitors p27 and p21 were significantly increased. Conclusion The present data demonstrates that MS-275 has the ability to induce apoptosis and suppress NPC proliferation and migration by affecting the JAK1/STAT3 signaling pathway. Therefore, MS-275 may present as a promising therapeutic agent for intractable NPC.