NPC has a remarkable ethnic and geographic distribution, with a high prevalence in southern China, Southeast Asia, Northern Africa, Greenland and Inuits of Alaska. The annual incidence peaks at 50 cases per 100,000 persons in endemic regions, but it is rare in the Western world. Epstein-Barr virus infection, environmental factors, and genetic susceptibility are associated with NPC. Cisplatin chemotherapy and radiotherapy are the main treatments for NPC. LY2835219 CDK inhibitor Unfortunately, many NPC patients do not benefit much from concurrent chemoradiotherapy; 30% to 40% of patients develop distant metastases within 4 years, and once metastasis occurs, the prognosis is very poor. Genetic alterations have been reported in NPC, and our recent findings showed that Jab1/CSN5 is overexpressed and negatively regulates p27 in NPC and contribute to radiotherapy and chemotherapy resistance. There is a JTP-74057 critical need to develop more effective treatments for NPC. Signal transducer and activator of transcription 3 is a member of a family of latent cytosolic transcription factors whose activation is contingent on the phosphorylation of a conserved tyrosine residue by upstream kinases such as Janus kinase 2. This event promotes the dimerization of STAT3 monomers via their Src homology-2 domains, rendering them in a transcriptionally active conformation. Persistent activation of the JAK2/STAT3 signaling pathway has been documented in a wide range of human solid and blood cancers and is commonly associated with worse prognoses. Among the Tumor-promoting activities ascribed to persistent STAT3 signaling are those involved with cell proliferation, metastasis, angiogenesis, host immune evasion, and resistance to apoptosis. STAT3 is constitutively activated and expressed in the nucleus in NPC cells and it has been reported that stat3 activation in NPC is induced by EBV encoded LMP1. Recently, it has been reported that STAT3 activation contributes directly to the invasiveness of nasopharyngeal cancer cells. Although STAT3 serves critical and necessary roles in early embryogenesis, its presence in the majority of normal adult cell types is largely dispensable, making it an attractive target for cancer therapy. Different approaches have been developed to effectively inhibit STAT3. In silico screenings to identify candidate nonpeptidic small molecules that inhibit STAT3 by binding directly to its Src homology 2 domain led to a whole new class of inhibitors. Of these, the commercially available inhibitor Stattic has been shown to selectively inhibit the function of the STAT3 SH2 domain regardless of STAT3 phosphorylation status. Stattic selectively inhibits activation, dimerization, and nuclear translocation of STAT3, resulting in an increase in apoptosis rates of STAT3-dependent cancer cells. Despite an abundance of work focused on the inhibition of Stat3 activation, the anti-tumor effects on NPC have not yet been reported. The purpose of this work is to provide an initial assessment of the potential therapeutic utility of STAT3 inhibition by Stattic in NPC. Our findings indicate that Stattic, through inhibition of STAT3 activation, reduces the growth and increases the apoptosis of NPC and sensitize NPC to cisplatin and IR.