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[Effects of FK866 on migration of A549 cells and related mechanism].

[Article in Chinese]

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.
3
Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.

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 IC50 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 ╬╝mol/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.

PMID:
30146805
[Indexed for MEDLINE]

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