Endostar suppresses invasion through downregulating the expression of matrix metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells.
Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence forming another his-tag structure, was approved by the State Food and Drug Administration of China (SFDA) in 2005 for the treatment of non-small-cell lung cancer. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we examined the anti-invasive activities of endostar in vitro. The results showed that endostar suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a concentration-dependent manner. It could inhibit the wound healing migration of MDA-MB-435 cells and invasion of MDA-MB-435 cells through reconstituted ECM (matrigel). Zymography revealed that endostar decreased the secretion of MMP-2 and MMP-9. Endostar could also inhibit the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells. Additionally, endostar exerted an inhibitory effect on the phosphorylation of ERK1/2. Collectively, these data provided a molecular basis for the anti-invasive effects of endostar.
Lu
Na
N
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 210009 Nanjing, People's Republic of China.
Ling
Yun
Y
Gao
Ying
Y
Chen
Yan
Y
Mu
Rong
R
Qi
Qi
Q
Liu
Wei
W
Zhang
Haiwei
H
Gu
Hongyan
H
Wang
Sen
S
Yang
Yong
Y
Guo
Qinglong
Q
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D043169:Endostatins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D043169:Endostatins; D011994:Recombinant Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522911:endostar protein