Study Of Nitroso-iron-sulfur Clusters In Antitumor Vascular Therapy

In this project,a series of toxic substances were produced by redox reaction between Roussin's black salt(RBS)and hydrogen peroxide,which was highly expressed in the microenvironment,to achieve the treatment of tumor.As a photosensitive substance,RBS has always been a NO donor material known for the production of NO by light in tumor research.However,for light is limited to the depth of penetration in tumor tissue.In this process,the problem of penetration depth of traditional light is overcome.It was found that NO,ROS and iron compound could be produced efficiently with hydrogen peroxide in dark conditions.According to the characteristics of the tumor microenvironment,such as high expression of hydrogen peroxide,lower p H,high expression of glutathione and abundant tumor blood vessels,combined with RBS,the following studies were carried out.Through cytotoxicity and trypan blue test,it was confirmed that RBS can also produce strong toxicity and kill cancer cells in a short time without light.However,in normal cells with low hydrogen peroxide expression,the cytotoxicity induced by RBS was lower than that of cancer cells by half inhibitory concentration analysis.After comparing the toxicity experiments of B16-F10 cells,AGS cells and HUVECs,this study selected B16-F10 to study the mechanism of cell death caused by RBS.It was found that RBS in tumor cells could produce ROS,NO,and cause DNA damage and decrease mitochondrial membrane potential,in addition to lipid peroxidation.In the establishment of tumor model,we first selected subcutaneous tumors of B16-F10 mice with abundant tumor blood vessels.Compared with the treatment group and control group,the growth of subcutaneous tumor in mice treated with RBS avoiding light was inhibited.The lung metastatic tumor model was further selected.The treatment group showed a certain therapeutic effect.The anti-tumor blood vessels and macrophages in vivo were demonstrated by the sections.