Abstract | BACKGROUND:
Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo- protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin- lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety. METHODS: RESULTS:
ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice. CONCLUSIONS:
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Authors | Wen-guo Jiang, Xin-an Lu, Bo-yang Shang, Yan Fu, Sheng-hua Zhang, Daifu Zhou, Liang Li, Yi Li, Yongzhang Luo, Yong-su Zhen |
Journal | BMC cancer
(BMC Cancer)
Vol. 13
Pg. 479
(Oct 15 2013)
ISSN: 1471-2407 [Electronic] England |
PMID | 24128285
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Endostatins
- LDP-endostatin N-terminal fusion protein
- Recombinant Fusion Proteins
- endostatin-LDP C-terminal fusion protein
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Topics |
- Animals
- Antineoplastic Agents
(pharmacokinetics, pharmacology, therapeutic use)
- Breast Neoplasms
(drug therapy, pathology)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Endostatins
(pharmacokinetics, pharmacology, therapeutic use)
- Endothelial Cells
(drug effects, physiology)
- Female
- Humans
- Lung
(metabolism)
- Lung Neoplasms
(drug therapy, secondary)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Recombinant Fusion Proteins
(pharmacokinetics, pharmacology, therapeutic use)
- Tissue Array Analysis
- Tissue Distribution
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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