Fu L X, Lian Q W, Pan J D, Xu Z L, Zhou T M, Ye B
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
J Biol Regul Homeost Agents. 2017 Jan-Mar;31(1):51-58.
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry. As a consequence, we found that JAK2 inhibitor AG490 inhibited cell growth and invasion, and induced cell apoptosis and cycle arrest in GBC-SD and SGC-996 cells. Furthermore, the expression levels of p-JAK2, p-STAT3, VEGFC-/-D and cyclinD1 were downregulated, while p53 expression was upregulated in AG490-treated GBC cells indicated by Western blot assay. Therefore, our findings demonstrate that JAK inhibitor AG490 inhibits growth and invasion of GBC cells via blockade of JAK2/STAT3 signaling and provides the potential therapeutic strategy for the treatment of GBC patients.
Janus激酶-信号转导子和转录激活子信号通路（JAK/STAT通路）在多种恶性肿瘤的发生发展过程中发挥着关键作用。以往研究表明，抑制JAK/STAT信号可阻断癌细胞的生长和转移，然而，JAK抑制剂AG490对胆囊癌（GBC）的抗肿瘤作用尚未见报道。我们目前的研究旨在通过MTT法、细胞集落形成实验、Transwell实验和流式细胞术，研究JAK抑制剂AG490对GBC细胞（GBC-SD和SGC-996）的细胞生长、侵袭潜能和凋亡的影响及相关机制。结果发现，JAK2抑制剂AG490抑制了GBC-SD和SGC-996细胞的生长和侵袭，并诱导了细胞凋亡和细胞周期阻滞。此外，蛋白质免疫印迹分析显示，在AG490处理的GBC细胞中，p-JAK2、p-STAT3、VEGFC-/-D和细胞周期蛋白D1的表达水平下调，而p53表达上调。因此，我们的研究结果表明，JAK抑制剂AG490通过阻断JAK2/STAT3信号抑制GBC细胞的生长和侵袭，为GBC患者的治疗提供了潜在的治疗策略。
