- Title
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An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway
- Authors
- Zhang, X., Zou, G., Li, X., Wang, L., Xie, T., Zhao, J., Wang, L., Jiao, S., Xiang, R., Ye, H., Shi, Y.
- Source
- Full text @
High throughput screening for compounds that act on the SerRS promoter. (A) Scheme of the dual luciferase reporter-based high throughput screening. (B) Heat map of the luciferase/Renilla ratios for 44 compounds responsive to the SerRS promoter. (C) The molecular structure of MEQ. (D) Relative firefly/Renilla (F/R) ratios for MEQ at indicated dosages and time points. Data are plotted as means ± SEM ( |
MEQ inhibits VEGFA expression by upregulating SerRS in cultured cells. (A, B) The qRT-PCR shows SerRS expression in MDA-MB-231 cells treated with MEQ at indicated dosages or with dimethyl sulfoxide (DMSO) as a vehicle control for 48 h (A) or treated with 10 μM MEQ for the indicated time periods (B). (C) Western blotting to show SerRS protein levels in MDA-MB-231 cells treated with the indicated dosages of MEQ or DMSO for 48 h. (D) The qRT-PCR shows SerRS expression in human umbilical vein endothelial cells (HUVECs) cells treated with 10 μM of MEQ for 48 h. (E, F) The qRT-PCR shows vascular endothelial growth factor A (VEGFA) expression in MDA-MB-231 cells treated with MEQ for the indicated time periods (E) and in HUVEC cells treated with 10 μM of MEQ for 48 h (F). (G) ELISA analyses of secreted VEGFA from MDA-MB-231 cells treated with 10 μM MEQ for 48 h. (H) Western blotting shows the knockdown efficiency of shRNA against SerRS (shSerRS) with a shRNA against |
MEQ inhibits angiogenesis |
MEQ suppressed the progression of breast cancer allografts in mice. (A) Scheme of mouse experiments based on the breast cancer allograft model. qod: quaque omni die. (B) Tumor growth curve. ( |
MEQ inhibits the growth of human triple-negative breast cancer (TNBC) xenografts in mice. (A) The growth curves of MDA-MB-231 xenografts in mice treated with MEQ or the dimethyl sulfoxide control. Data are plotted as the mean ± SD. (B, C) At 30 days post-inoculation, the xenografts were dissected and weighted, |
MEQ targets MTA2 to regulate SerRS expression. (A) Dual-luciferase reporter assay for biotin-conjugated MEQ (MEQ-biotin). Values are the mean ± SEM. ns, not significant, *** |
Mechanistic model to show how MEQ inhibits triple-negative breast cancer (TNBC) angiogenesis by regulating the MTA2/SerRS/VEGFA axis. The MTA2-containing NuRD deacetylase complex binds to the |