Inhibition of Endothelial Cell Proliferation and Tumor Angiogenesis by Up-Regulating NDRG2 Expression in Breast Cancer Cells.

PLoS One. 2012; 7(2): e32368
Ma J, Liu W, Yan X, Wang Q, Zhao Q, Xue Y, Ren H, Wu L, Cheng Y, Li S, Miao L, Yao L, Zhang J

The N-myc downstream-regulated gene 2 (NDRG2) is concerned in tumor cell differentiation as well as apoptosis, though its function in tumor angiogenesis remains to be established. Here, we employed adenovirus overexpressing NDRG2 (Ad-NDRG2) to efficiently up-regulate target gene expression in a NDRG2-low-expressing, breast cancer cell line MCF-7. Moreover, VEGF secretion was decreased in MCF-7 cells putrescent by Ad-NDRG2, as well as medium conditioned by these putrescent cells could significantly inhibit a proliferation, tube formation as well as advance of tellurian umbilical vein endothelial cells (HUVECs). Further study indicated that a angiogenesis promoting factors VEGF as well as HIF-1 were down-regulated, whereas a angiogenesis suppressing factors p53 as well as VHL were up-regulated in MCF-7 cells putrescent by Ad-NDRG2. Finally, in a nude rodent model, intratumoral injections of Ad-NDRG2 every 3 days for 20 days significantly inhibited a expansion as well as angiogenesis of xenografted MCF-7 tumors. In summary, these data indicate that NDRG2 may be concerned in angiogenesis by impacting a expression of angiogenesis associated factors. Thus, specific overexpression of NDRG2 by adenovirus represents a promising approach for a treatment of tumor angiogenesis.

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