Inhibitory effect of AG490 on invasion and metastasis of human pancreatic cancer cells in vitro.
- Author:
Chen HUANG
1
;
Zheng-Jun QIU
;
Jun CAO
;
Ke-Jian HUANG
;
Fang ZHANG
;
Tao JIANG
;
Lin ZHU
;
Jun LIU
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Blotting, Western; Cell Line, Tumor; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; drug effects; Humans; Janus Kinases; antagonists & inhibitors; Matrix Metalloproteinase 2; genetics; metabolism; Neoplasm Invasiveness; Neoplasm Metastasis; Pancreatic Neoplasms; genetics; metabolism; pathology; Phosphorylation; drug effects; RNA, Messenger; biosynthesis; genetics; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; metabolism; Signal Transduction; drug effects; Tyrphostins; pharmacology; Vascular Endothelial Growth Factor A; genetics; metabolism
- From: Chinese Journal of Oncology 2006;28(12):890-893
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect and mechanism of blockade of STAT3 signaling pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human highly metastatic pancreatic cancer line SW1990 in vitro.
METHODSAG490 was added into the culture media for SW1990 cells. The invasion ability of SW1990 cells was determined by cell invasion assay kit. Western blot was performed to detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2 and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.
RESULTS20 micromol/L AG490 significantly inhibited the invasion ability of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79) %. The use of AG490 not only markedly reduced the protein expression of p-STAT3, MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.
CONCLUSIONBlocking STAT3 activation with AG490 can inhibit the invasion and metastasis ability of pancreatic cancer cells in vitro through down-regulation of MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel strategy in prevention of invasion and metastasis of pancreatic cancer.
