Metformin inhibits proliferation and promotes apoptosis of HER-2 positive breast cancer cells possibly through the Hippo-YAP pathway.
10.12122/j.issn.1673-4254.2022.05.16
- Author:
Yu XU
1
;
Ting XU
1
;
Yuan Feng XIONG
1
;
Jia Yi HUANG
1
Author Information
1. Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
- Publication Type:Journal Article
- Keywords:
HER-2 positive breast cancer;
Hippo-YAP pathway;
SKBR3 cells;
metformin
- MeSH:
Apoptosis;
Cadherins;
Cell Proliferation;
ErbB Receptors;
Fibronectins;
Metformin/pharmacology*;
Neoplasms;
Protein Serine-Threonine Kinases;
RNA, Messenger;
Transcription Factors/metabolism*;
Vimentin
- From:
Journal of Southern Medical University
2022;42(5):740-746
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of metformin on the proliferation and apoptosis of HER-2-positive breast cancer cell line SKBR3 and explore the possible mechanism of its action.
METHODS:SKBR3 cells were treated with different concentrations (20-120 μmol/L) of metformin, and the changes in cell proliferation and colony formation ability were assessed using CCK-8 assay and crystal violet staining, respectively. Flow cytometry was performed to analyze cell apoptosis and cell cycle changes. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect mRNA expressions of YAP, TAZ, EGFR, CTGF, CYR61, E-cadherin, N-cadherin, vimentin and fibronectin in the treated cells, and the protein expressions of YAP and TAZ were detected using Western blotting; immunofluorescence assay was used to observe YAP/TAZ nuclear translocation in the cells.
RESULTS:Metformin treatment significantly inhibited the proliferation of SKBR3 cells (P < 0.05) in a concentration- and time-dependent manner. The results of flow cytometry showed that metformin significantly promoted apoptosis and caused cell cycle arrest at G1 phase in SKBR3 cells. Metformin treatment significantly down-regulated the mRNA expressions of YAP, TAZ, EGFR, CTGF and CYR61, N-cadherin, vimentin and fibronectin (P < 0.05) and up-regulated the expression of E-cadherin (P < 0.05); Western blotting results showed that YAP and TAZ protein expressions were significantly down-regulated in the cells after metformin treatment (P < 0.05). Immunofluorescence assay revealed that metformin treatment caused the concentration of YAP and TAZ in the cytoplasm, and significantly reduced their amount in the cell nucleus.
CONCLUSION:Metformin can inhibit proliferation and promote apoptosis and epithelal-mesenchymal transition of HER-2 positive breast cancer cells possibly by that inhibing YAP and TAZ expression and their nuclear localization.
