title: Endostar suppresses invasion through downregulating the expression of matrix metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 210009 Nanjing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Mu
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Gu
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: 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
chemical_list: D043169:Endostatins; D011994:Recombinant Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522911:endostar protein