1. Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer
- Author
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Xiaolong Zou, Xian Jiang, Xuesong Dong, Haiquan Qiao, Xueying Sun, and Hongchi Jiang
- Subjects
Vascular Endothelial Growth Factor A ,Colorectal cancer ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,lcsh:Medicine ,Down-Regulation ,Mice, Nude ,Biology ,Transfection ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Molecular Biology ,Regulation of gene expression ,Biochemistry, medical ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,Research ,Biochemistry (medical) ,lcsh:R ,Calcium-Binding Proteins ,General Medicine ,Cell Biology ,Genetic Therapy ,medicine.disease ,Molecular biology ,Neoplasm Proteins ,Vascular endothelial growth factor ,Endothelial stem cell ,Gene Expression Regulation, Neoplastic ,Vascular endothelial growth factor A ,chemistry ,Cell culture ,Colonic Neoplasms ,Cancer research ,Carrier Proteins ,Cell Adhesion Molecules - Abstract
Developmentally regulated endothelial cell locus-1 (Del1) is an embryonic angiogenic factor expressed in early embryonic endothelial cells, but recently has been found to be expressed in some forms of cancers including colon and breast cancers, and melanoma, and human cancer cell lines. Overexpression of Del1 accelerates tumor growth by enhancing vascular formation, implying Del1 may be a potential target for anti-angiogenic cancer therapy. The study aims to investigate whether downregulation of Del1 could inhibit the growth of tumors established in nude Balb/c mice by subcutaneous implantation of human LS-174T colon cancer cells. The shRNA expression vectors targeting human Del1, and vascular endothelial growth factor (VEGF) were constructed. Gene transfection of Del1-shRNA downregulated expression of Del1 in LS-174T cells in vivo and in vitro, but did not alter the proliferative or survival properties of cells in vitro. Gene transfection of VEGF-shRNA downregulated expression of both VEGF and Del1 in LS-174T cells in vivo and in vitro. Both Del1-shRNA and VEGF-shRNA gene therapies exhibited anti-tumor activities and they also showed a synergistic effect in suppressing growth of colon tumors by anti-angiogenesis and anti-proliferation. Although further investigation to clarify the mechanisms explaining the role of Del1 in tumor growth, and the interaction between VEGF and Del1, is required, the results indicate that downregulation of Del1 presents a potent therapeutic strategy to combat colon cancer.
- Published
- 2008