Study Of Anti-tumor Angiogenesis And Inhibitors Of AD By Ruthenium Complex, Multi-molybdenum Polyoxometalates Nanocrystalline

In this paper, on the basis of previous synthesis of Mo-O-based polyoxometalates andruthenium complexes, we study these complexes whether they have brought anti-tumor effectby anti-angiogenesis and inhibited Alzheimer’s disease-related protein Aβ40amyloidaccumulation and fibrosis under a variety of different research methods. This text is dividedinto four parts.The first chapter is the introduction, in this chapter it mainly talks about factors related totumor growth, metastasis, and angiogenesis, including the content: human umbilical veinendothelial cells (HUVECs); angiogenic growth factor (VEGF) and mechanism of action; theanti-angiogenic drugs research and anti-angiogenesis research methods at present. Followedby a brief introduction of the the polyoxometalate biological functions and research progress,then introduced the research progress of Alzheimer’s disease-related protein Aβ to clarify thebackground and significance of this topic.The main work of chapter II is accomplished by the MTT assay, in vitro and in vivoanti-angiogenesis experiments, apoptosis experiments, and apoptosis mechanisms andsignaling pathways experimental to study three multi-molybdenum polyoxometalates (1,2,3)whether aim vascular endothelial growth factor VEGF play as a target for anti-tumor effect.The experimental results showed that the three multi-molybdenum polyoxometalates caneffectively inhibit VEGF mediated angiogenesis in vitro and in vivo, and by active transportinto HUVECs, caused via the interaction of oxidative damage and induce apoptosis ofHUVECs cells in the cytoplasm of mitochondria and other organelles, play down theexpression of PI3K/Akt and MAPK/Erk, inhibiti the proliferation and migration of HUVECs,thus play the anti-tumor effect. The inhibition of the complex3is the most obvious.In chapter III, it is based on the previous studies which confirmed the anti-angiogenesisof RBD and RPD, using flow cytometry, laser scanning confocal microscopy and nitratereductase experiments found that RBD and RPD mainly enter into HUVECs via activetransport, and mainly gather in the cytoplasm and around the nucleus. Besides, they dissipatedthe mitochondrial membrane potential, increased in the level of reactive oxygen species and reduced the level of NO, thus result in oxidative damage. The further analysis showed that theRBD and RPD induced apoptosis was mainly due to oxidative damage. It provides atheoretical basis for the ruthenium complexes in the anti-vascular research.In chapter IV, it is found that multi-molybdenum polyoxometalates (1,2,3) can effectivelyinhibit the Aβ40itself or the metal ion-induced aggregation and fibrosis, and can reduce thecytotoxicity of Aβ40, and has a protective effect on PC12cells by ThT fluorescenceexperiment, turbidity experiments, circular dichroism (CD experiments), transmission electronmicroscopy (TEM) experiments and cytotoxicity assays. Thus, the futher study on themechanism of Aβ40generated toxicity on the PC12cells found that oxidative damage mayshare of the a major position. This provided a theoretical basis for the study of thepolyoxometalate in anti-Alzheimer’s disease.