Inhibition of the Signal Transducers and Activators of Transcription (STAT) 3 Signalling Pathway by AG490 in Laryngeal Carcinoma Cells

摘要

Signal transducers and activators of transcription (STAT) are important in the development of laryngeal carcinomas and are potential novel molecular targets for therapy to improve survival of patients with this cancer. This study was designed to investigate the influence of the janus activated kinase (JAK)/STAT inhibitor AG490 on proliferation and apoptosis of Hep-2 human laryngeal cancer cells and whether there was any inhibition by AG490 of the JAK/STAT3 signalling pathway. AG490 inhibited cell proliferation in dose-and time-dependent manners and induced apoptosis in Hep-2 cells, with the number of apoptotic cells increasing with time. AG490 inhibited G1 to S cell cycle transition and induced G1 cell cycle arrest as well as significantly down-regulating STAT3, phosphorylated STAT3 and survivin in Hep-2 cells. This study showed that AG490 significantly inhibited proliferation and induced apoptosis of laryngeal carcinoma cells through down-regulation of STAT3 and survivin, suggesting a potential target for laryngeal carcinoma treatment.