Zhang H, Zhang D, Luan X, Xie G, Pan X
Department of Otorhinolaryngology, Head and Neck Surgery, Qilu Hospital, Shandong University, Jinan, China.
J Int Med Res. 2010 Sep-Oct;38(5):1673-81. doi: 10.1177/147323001003800512.
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.
信号转导和转录激活因子(STAT)在喉癌的发展中起重要作用,并且是改善该癌症患者生存率的潜在新型分子治疗靶点。本研究旨在探讨janus激活激酶(JAK)/STAT抑制剂AG490对人喉癌细胞Hep-2增殖和凋亡的影响,以及AG490是否对JAK/STAT3信号通路有抑制作用。AG490以剂量和时间依赖性方式抑制细胞增殖,并诱导Hep-2细胞凋亡,凋亡细胞数量随时间增加。AG490抑制G1期到S期的细胞周期转换,诱导G1期细胞周期停滞,并显著下调Hep-2细胞中的STAT3、磷酸化STAT3和生存素。本研究表明,AG490通过下调STAT3和生存素显著抑制喉癌细胞的增殖并诱导其凋亡,提示其可能成为喉癌治疗的一个靶点。