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Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer.

Zou X, Qiao H, Jiang X, Dong X, Jiang H, Sun X - J. Biomed. Sci. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Hepatosplenic Surgery Center, Department of General Surgery, The First Clinical College of Harbin Medical University, Harbin 150001, PR China. zouxiaolongbs@163.com

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.

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shRNA gene therapy inhibits growth of tumors. LS-174T tumors were established. When the tumors reached around 100 mm3 (indicated by a vertical arrow), they were injected with control vector, Del1-shRNA, VEGF-shRNA, or a combination of Del1-shRNA plus VEGF-shRNA, and their sizes (mm3) were monitored and recorded. The untreated tumors also served as controls. A significant difference in tumor volumes from control is denoted by "*", and a highly significant difference by "†". "‡" Indicates significant difference from Del1-shRNA or VEGF-shRNA monotherapies.
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Figure 3: shRNA gene therapy inhibits growth of tumors. LS-174T tumors were established. When the tumors reached around 100 mm3 (indicated by a vertical arrow), they were injected with control vector, Del1-shRNA, VEGF-shRNA, or a combination of Del1-shRNA plus VEGF-shRNA, and their sizes (mm3) were monitored and recorded. The untreated tumors also served as controls. A significant difference in tumor volumes from control is denoted by "*", and a highly significant difference by "†". "‡" Indicates significant difference from Del1-shRNA or VEGF-shRNA monotherapies.

Mentions: Established LS-174T tumors (100 mm3) were intratumorally injected with either control vector, Del1-shRNA, VEGF-shRNA or Del1-shRNA + VEGF-shRNA expression plasmids complexed with FuGENE™ 6. The untreated tumors also served as control. The untreated tumors and the tumors treated with control vector grew remarkably fast reaching 623.1 ± 68.9 mm3 and 645.2 ± 74.5 mm3 in volume, respectively, three weeks after treatments. In contrast, tumors treated with Del1-shRNA or VEGF-shRNA plasmids reached only 501.7 ± 60.3 or 443.6 ± 47.8 mm3 in volume, respectively, at the same time point (Figure 3). A combination of Del1-shRNA and VEGF-shRNA further suppressed tumor growth such that tumors reached only 158.4 ± 33.9 mm3 in volume (Figure 3), indicating the synergistic effects of Del1-shRNA and VEGF-shRNA.


Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer.

Zou X, Qiao H, Jiang X, Dong X, Jiang H, Sun X - J. Biomed. Sci. (2008)

shRNA gene therapy inhibits growth of tumors. LS-174T tumors were established. When the tumors reached around 100 mm3 (indicated by a vertical arrow), they were injected with control vector, Del1-shRNA, VEGF-shRNA, or a combination of Del1-shRNA plus VEGF-shRNA, and their sizes (mm3) were monitored and recorded. The untreated tumors also served as controls. A significant difference in tumor volumes from control is denoted by "*", and a highly significant difference by "†". "‡" Indicates significant difference from Del1-shRNA or VEGF-shRNA monotherapies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666667&req=5

Figure 3: shRNA gene therapy inhibits growth of tumors. LS-174T tumors were established. When the tumors reached around 100 mm3 (indicated by a vertical arrow), they were injected with control vector, Del1-shRNA, VEGF-shRNA, or a combination of Del1-shRNA plus VEGF-shRNA, and their sizes (mm3) were monitored and recorded. The untreated tumors also served as controls. A significant difference in tumor volumes from control is denoted by "*", and a highly significant difference by "†". "‡" Indicates significant difference from Del1-shRNA or VEGF-shRNA monotherapies.
Mentions: Established LS-174T tumors (100 mm3) were intratumorally injected with either control vector, Del1-shRNA, VEGF-shRNA or Del1-shRNA + VEGF-shRNA expression plasmids complexed with FuGENE™ 6. The untreated tumors also served as control. The untreated tumors and the tumors treated with control vector grew remarkably fast reaching 623.1 ± 68.9 mm3 and 645.2 ± 74.5 mm3 in volume, respectively, three weeks after treatments. In contrast, tumors treated with Del1-shRNA or VEGF-shRNA plasmids reached only 501.7 ± 60.3 or 443.6 ± 47.8 mm3 in volume, respectively, at the same time point (Figure 3). A combination of Del1-shRNA and VEGF-shRNA further suppressed tumor growth such that tumors reached only 158.4 ± 33.9 mm3 in volume (Figure 3), indicating the synergistic effects of Del1-shRNA and VEGF-shRNA.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Hepatosplenic Surgery Center, Department of General Surgery, The First Clinical College of Harbin Medical University, Harbin 150001, PR China. zouxiaolongbs@163.com

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.

Show MeSH
Related in: MedlinePlus