Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism.
- Author:
Lei YUAN
1
;
Wen-Juan FAN
;
Xu-Guang YANG
;
Shu-Mei RAO
;
Jin-Ling SONG
;
Guo-Hua SONG
Author Information
1. Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China. lhyzsgh@163.com.
- Publication Type:Journal Article
- MeSH:
Breast Neoplasms;
pathology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Cyclin-Dependent Kinase Inhibitor p21;
metabolism;
Female;
Humans;
Imidazoles;
pharmacology;
Insulin-Like Growth Factor Binding Proteins;
pharmacology;
Phosphorylation;
Pyridines;
pharmacology;
Signal Transduction;
Somatomedins;
p38 Mitogen-Activated Protein Kinases;
antagonists & inhibitors;
metabolism
- From:
Acta Physiologica Sinica
2013;65(5):519-524
- CountryChina
- Language:Chinese
-
Abstract:
The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.
