The effects of luminescent ruthenium(II) polypyridyl functionalized selenium nanoparticles on bFGF-induced angiogenesis and AKT/ERK signaling.
Anti-angiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Thus, blocking angiogenesis could be a strategy to arrest tumor growth. The function and mechanism of luminescent ruthenium-modified selenium nanoparticles (Ru-SeNPs) in angiogenesis have not been elucidated to date. Here, we found that Ru-SeNPs significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration and tube formation. Ru-SeNPs was also tested in vivo in the chicken chorioallantoic membrane (CAM) assay and found to inhibit bFGF-treated CAMs development like suramin. Moreover, we showed that Ru-SeNPs inhibited the activations of FGFR1 and its downstream protein kinases, such ErK and AKT. Furthermore, by using fluorescence confocal microscopy and TEM imaging studies, we have demonstrated their cellular uptake and localization within the cytoplasm of HepG2 and HUVEC cells. These findings indicate that Ru-SeNPs inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis and anticancer therapies.
Department of Chemistry, Jinan University, Guangzhou 510632, China.
Dongdong
D
Sun
Yanan
Y
Liu
Qianqian
Q
Yu
Yanhui
Y
Zhou
Rong
R
Zhang
Xiaojia
X
Chen
An
A
Hong
Jie
J
Liu
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D002942:Circular Dichroism; D004705:Endocytosis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D020128:Inhibitory Concentration 50; D008163:Luminescent Measurements; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011418:Prophase / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry*
D017304:Annexin A5; D011725:Pyridines; D016222:Fibroblast Growth Factor 2; D012428:Ruthenium; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D012643:Selenium