Inhibition of vinorelbine on invasion and metastasis of breast cancer cell and its mechanism
10.7501/j.issn.0253-2670.2013.13.016
- Author:
Yi-Ping MA
1
Author Information
1. Tianjin Huanhu Hospital
- Publication Type:Journal Article
- Keywords:
Epithelial-mesenchymal transition expression;
Human breast cancer MCF-7 cells;
Human breast cancer MDA-MB-435 cells;
Signaling pathway;
Tumor metastasis;
Vinorelbine
- From:
Chinese Traditional and Herbal Drugs
2013;44(13):1786-1792
- CountryChina
- Language:Chinese
-
Abstract:
The MCF-7 and MDA-MB-435 cells were treated with 1 and 10 μmol/L VRB. The cell adhesion was tested by MTS, the invasion was detected by Transwell, secretion of TGF-β was detected using ELISA, the activities of MMP-2 and MMP-9 were detected by zymography, the expression of proteins, including E-cadherin (E-CAD), N-cadherin (N-CAD), MMP-2, and MMP-9, p-JNK and, p-Akt was evaluated by Western blotting, RT-PCR was used to detect E-CAD, N-CAD, MMP-2, and MMP-9 genes, and dual-luciferase reporter assay was used to validate the activities of AP-1 and NF-κB. Results After being treated with 1 and 10 μmol/L VRB, for MCF-7 and MDA-MB-435, the adhesion ability was decreased by 34.8% and 66.8%, 42.6% and 72.3%; The metastatic ability was decreased by 44.4% and 72.2%, 47.7% and 86.4%; The secretion of TGF-β was reduced by 28.2% and 52.1%, 39.0% and 55.1%, significantly; The mRNA expression levels of E-CAD were increased by 86.5% and 181.6%, 116.6% and 160.7%; while the levels of N-CAD were decreased by 33.7% and 74.1%, 57.6% and 76.9%; The gene expression of MMP-2 was decreased by 71.6% and 88.4%, 57.4% and 69.4%; The gene expression of MMP-9 was decreased by 15.0% and 84.0%, 22.1% and 73.0%, respectively. The protein expression of E-CAD was up-regulated while the protein expression of N-CAD, MMP-2, MMP-9, p-JNK, and p-Akt were down-regulated significantly; And dual-luciferase reporter assay validated VRB could inhibit the transcriptional activity of AP-1 and NF-κB by 27.7% and 68.2%, 34.8% and 71.4%, 18.4% and 44.8%, 24.4% and 51.9%, respectively. Conclusion VRB could inhibit the metastasis of breast cancer MCF-7 and MDA-MB-435 cells via down-regulation of inhibition and blocking of signaling pathway correlated with metastasis and epithelial-mesenchymal transition.
