JAK2 tyrosine kinase inhibitor AG490 suppresses cell growth and invasion of gallbladder cancer cells via inhibition of JAK2/STAT3 signaling.
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.
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
L X
LX
Fu
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Q W
QW
Lian
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
J D
JD
Pan
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Z L
ZL
Xu
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
T M
TM
Zhou
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
B
B
Ye
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016159:Tumor Suppressor Protein p53; D020032:Tyrphostins; C467486:VEGFC protein, human; C579459:VEGFD protein, human; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D019938:Cyclin D1; C507924:JAK2 protein, human; D053614:Janus Kinase 2