Role of NF-κB in factor VIIa-induced proliferation and migration of colon cancer cell line SW620 cells.
- Author:
Dong-lin GUO
1
;
Hong ZHOU
;
Ying WU
;
Fang ZHOU
;
Xian-mei ZHANG
;
Guo-ying XU
;
Hai-ping WEN
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Caspase 7; genetics; metabolism; Cell Line, Tumor; Cell Movement; drug effects; Cell Proliferation; drug effects; Colonic Neoplasms; metabolism; pathology; Factor VIIa; pharmacology; Humans; I-kappa B Proteins; metabolism; Interleukin-8; genetics; metabolism; NF-KappaB Inhibitor alpha; Proline; analogs & derivatives; pharmacology; RNA, Messenger; metabolism; Receptor, PAR-2; metabolism; Thiocarbamates; pharmacology; Thromboplastin; genetics; metabolism; Transcription Factor RelA; antagonists & inhibitors; metabolism
- From: Chinese Journal of Oncology 2011;33(9):649-653
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the roles of NF-κB in factor VIIa-induced proliferation and migration of a colon cancer cell line (SW620) in vitro and its possible mechanism.
METHODSThe expression levels of NF-κB (p65), inhibitory protein of NF-κB (IκB-α), caspase-7, interleukin 8 (IL-8) and tissue factor (TF) in SW620 cells treated with factor VIIa, PDTC (an inhibitor of NF-κB) and other factors were measured by Western-blotting and real-time PCR. Proliferation and migration of the cells were analyzed by flow cytometry and Transwell assay, respectively.
RESULTSFactor VIIa down-regulated the IκB-α level in SW620 cells and increased the intranuclear level of NF-κB. Those effects of factor VIIa were blocked by anti-TF or anti-PAR2 antibodies. The effects of factor VIIa on proliferation and migration of SW620 cells, expression of IL-8, TF as well as caspase-7, were interfered by PDTC (the inhibitor of NF-κB).
CONCLUSIONSTF/VIIa complex activates NF-κB pathway via PAR2, thereby up-regulates IL-8 and down-regulates caspase-7 expression in SW620 cells, finally promotes proliferation and migration of colon cancer cells. In addition, TF/VIIa/PAR2/NF-κB pathway also upregulates TF expression, thus to create a positive feedback loop of TF/VIIa/PAR2/NF-κB/TF.