Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis

摘要: Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis antitumor activities in several animal models. specifically targets tumor vasculature to block growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) a non-covalently bound apo-protein (LDP), is member chromoprotein family antibiotics with extremely potent cytotoxicity cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing may obtain the combined capability targeting by respective ES LDM moiety. In this study, designed obtained two new endostatin-based proteins, endostatin-LDP (ES-LDP) LDP-endostatin (LDP-ES). vitro, antiangiogenic effect was determined wound healing assay formation their enediyne-energized analogs evaluated CCK-8 assay. Tissue microarray used analyze binding affinity LDP, or ES-LDP specimens human lung tissue tumor. The vivo efficacy carcinoma PG-BE1 xenograft experimental metastasis model 4T1-luc breast cancer. LDP-ES disrupted structures inhibited migration. Evidently, accumulated suppressed growth metastasis. show higher than LDP carcinoma; addition, share similar capability. Furthermore, protein ES-LDP-AE demonstrated significant against athymic mice. ES-based therapy provides some fundamental information for further drug development. Targeting both cells probably promising modality therapy.