Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer.
Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer.
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发育调节内皮细胞 locus-1 的下调抑制结肠癌的生长
DOI：
10.1186/1423-0127-16-33
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发表时间：
2009
影响因子：
11
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Zou X;Qiao H;Jiang X;Dong X;Jiang H;Sun X
发育调节内皮细胞基因座-1(Del1)是一种在早期胚胎内皮细胞中表达的胚胎血管生成因子，但最近发现在某些形式的癌症中也有表达，包括结肠癌、乳腺癌、黑色素瘤和人类癌细胞系。Del1过表达通过促进血管形成加速肿瘤生长，提示Del1可能成为抗血管生成肿瘤治疗的潜在靶点。本研究旨在探讨Del1基因下调是否能抑制人LS-174T结肠癌裸鼠皮下移植瘤的生长。构建了针对人Del1和血管内皮生长因子(VEGF)的shRNA表达载体。转导Del1-shRNA基因可下调体外培养的LS-174T细胞中Del1的表达，但不改变细胞的增殖和存活特性。体外和体内实验表明，基因转染可下调LS-174T细胞中血管内皮生长因子和Del1的表达。Del1-shRNA和VEGF-shRNA基因治疗均显示出抗肿瘤活性，并通过抗血管生成和抗增殖而显示出协同抑制结肠癌生长的作用。虽然还需要进一步的研究来阐明Del1在肿瘤生长中的作用机制，以及VEGF和Del1之间的相互作用，但结果表明，下调Del1的表达为对抗结肠癌提供了一种有效的治疗策略。
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 cellsin vivoandin vitro, but did not alter the proliferative or survival properties of cellsin vitro. Gene transfection of VEGF-shRNA downregulated expression of both VEGF and Del1 in LS-174T cellsin vivoandin 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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影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
2.4
作者：
Niu, Ji Xiao;Zhang, Wen Jian;Lou, Jin Ning
通讯作者：
Lou, Jin Ning
DOI：
10.1016/j.bbrc.2005.06.009
发表时间：
2005-08-05
影响因子：
3.1
作者：
Aoki, M;Kanamori, M;Kimura, T
通讯作者：
Kimura, T
影响因子：
8.8
作者：
Oehler MK;Bicknell R
通讯作者：
Bicknell R