@entity8185 targets XXXX via the NF-kB pathway in endothelial cells to inhibit angiogenesis.

@entity1992 @entity11132 @entity2479 @entity19 @entity5 @entity17727 @entity8185 @entity4601
The anti-malarial agent @entity8185 ( @entity4601 ) has strong anti-angiogenic activity. This study aimed to investigate the molecular mechanism underlying this effect of @entity4601 on angiogenesis. We found that @entity4601 shows a dose-dependent inhibition of proliferation and migration of in HUVECs. @entity4601 specifically down-regulates the mRNA and protein expression of @entity11132 in endothelial cells. Treatment with @entity4601 increases IkB-a protein and blocks nuclear translocation of NF-kB @entity1992 . In addition, @entity4601 directly regulates @entity11132 promoter activity through @entity1992 binding motif, and decreases the binding activity of @entity1992 and @entity11132 promoter, suggesting defective NF-kB signaling may underlie the observed effects of @entity4601 on @entity11132 expression. In the presence of the NF-kB inhibitor @entity17727 , @entity4601 could not further repress @entity11132 . Co-treatment with @entity17727 and @entity4601 produced minimal changes compared to the effects of either drug alone in in vitro angiogenesis assays. Similar findings were found in vivo through a @entity19 @entity2479 model examining the effects of @entity17727 and @entity4601 . Our data suggested that @entity4601 inhibits angiogenesis largely through repression of the NF-kB pathway. @entity4601 is well tolerated, and therefore may be an ideal candidate to use clinically as an angiogenesis inhibitor for @entity5 treatment.
