Effects of FK866 on migration of A549 cells and related mechanism.
- Author:
Xian XIE
1
;
Xiaofang XU
2
;
Qi WANG
2
;
Yunbi LU
1
;
Ming WU
2
;
Weiping ZHANG
1
Author Information
1. Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
2. Department of Thoracic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
- Publication Type:Journal Article
- MeSH:
A549 Cells;
Cadherins;
genetics;
Cell Movement;
drug effects;
Gene Expression Regulation;
drug effects;
Humans;
Morpholines;
pharmacology;
Neurokinin-1 Receptor Antagonists;
pharmacology;
Nicotinamide Phosphoribosyltransferase;
antagonists & inhibitors;
Piperazines;
pharmacology;
Vimentin;
genetics
- From:
Journal of Zhejiang University. Medical sciences
2018;47(1):1-9
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:: To investigate the effect of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 on the migration of human non-small cell cancer A549 cells and related mechanism.
METHODS:: The inhibition effect of FK866 on A549 cells was tested by MTT assay. A549 cells were treated with 1.0 and 10.0 nmol/L FK866, and the cell migration was evaluated by modified wound scratch assay. The mRNA expression of E-cadherin and vimentin was detected by real-time RT-PCR, and the expression of ERK1/2 and pERK1/2 was determined by Western blotting.
RESULTS:: FK866 inhibited the proliferation of A549 cells in a time-and concentration-dependent manner; after treatment for 72 h, the IC of FK866 was 9.55 nmol/L. When 1.0 nmol/L or 10.0 nmol/L FK866 was continuously applied 48 h before and 48 h after a scratch was made in wound scratch assay, the migration of A549 cells was significantly inhibited. However, when the FK866 was applied only 48 h after the scratch, the migration of A549 cells was inhibited by 10.0 nmol/L but not by 1.0 nmol/L FK866. The mRNA expression of E-cadherin and vimentin, and the activated ERK1/2 were significantly increased after 1.0 nmol/L FK866 treatment for 72 h. The pretreatment with nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide(1.0 mmol/L) or ERK1/2 inhibitor U0126 (10.0 μmol/L) reversed the up-regulation of E-cadherin and vimentin expression induced by FK866.
CONCLUSIONS:s: Low concentration of FK866 decreases the migration of A549 cells through the inhibition of NAD level, activation of ERK1/2 and up-regulation of E-cadherin expression. However, it also up-regulates the expression of vimentin, indicating that it may have dual effects on the migration of tumor cells.
