Mechanisms for quercetin in prevention of lung cancer cell growth and metastasis.
10.11817/j.issn.1672-7347.2015.06.004
- Author:
Xin ZHAO
1
;
Jian ZHANG
2
Author Information
1. Department of Respiration,First Affi liated Hospital, Xinxiang Medical University, Xinxiang Henan 453000, China.
2. Pediatric Intensive Care Unit, First Affiliated Hospital, Xinxiang Medical University, Xinxiang Henan 453000, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Cell Line, Tumor;
drug effects;
Down-Regulation;
Humans;
Lung Neoplasms;
pathology;
Matrix Metalloproteinase 9;
metabolism;
Matrix Metalloproteinase Inhibitors;
pharmacology;
Neoplasm Metastasis;
Quercetin;
pharmacology;
RNA, Messenger;
metabolism;
Tissue Inhibitor of Metalloproteinase-1;
pharmacology;
Transforming Growth Factor beta1;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2015;40(6):592-597
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effect of quercetin, an inhibitor of matrix metalloproteinases 9 (MMP-9), on the growth and metastasis of lung cancer cells and the underlying mechanisms.
METHODS:We evaluated the inhibitory effect and the inhibitory kinetics of quercetin on MMP-9 by ELISA and enzyme inhibition kinetics, and the inhibitory effect of quercetin on the growth of lung cancer cell (A549) by MTT. The effect of quercetin on levels of MMP-9 (mRNA and protein) and TGF-β1 (protein) in A549 were measured by RT-PCR and Western blot, respectively. The synergistic inhibition effect of quercetin plus TIMP-1 on the growth of lung cancer cell A549 was discussed.
RESULTS:Quercetin induced the apoptosis of A549. It was a reversible competitive inhibitor of MMP-9 (half inhibition rate IC50 of 5.25 μmol/L, inhibition constant Ki was 2.18 μmol/L). With the increase in quercetin concentration, the levels of MMP-9 (mRNA and protein) and TGF-β1 (protein) were decreased, and the number of tumor cells on wear filter membrane was reduced. The combination of quercetin (at low concentrations) with TIMP-1 showed synergistic inhibitory effect on the growth of A549 cells.
CONCLUSION:Quercetin is a competitive inhibitor of MMP-9 and could downregulate the expression of MMP-9 and TGF-β1, which plays an important role in A549 apoptosis.