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ORIGINAL RESEARCH ARTICLE

Endostar Suppresses Invasion Through Downregulating the Expression of Matrix Metalloproteinase-2/9 in MDA-MB-435 Human Breast Cancer Cells

Na Lu^*, Yun Ling^*, Ying Gao^*, Yan Chen^*, Rong Mu^*, Qi Qi^*, Wei Liu^*, Haiwei Zhang^*, Hongyan Gu^*, Sen Wang, Yong Yang^*,1 and Qinglong Guo^*,,1

^* Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 210009 Nanjing, People’s Republic of China; Jiangsu Simcere Pharmaceutical Research Co., Ltd., 210042 Nanjing, People’s Republic of China; and Jiangsu Center for Pharmacodynamics Research and Evaluation, 210009 Nanjing, People’s Republic of China

To whom requests for reprints should be addressed at ¹ Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 210009 Nanjing, People’s Republic of China. E-mail: anticancer_drug{at}yahoo.com.cn

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.

Key Words: endostar • invasion • MMP-2 • MMP-9