Preparation of dual ligand modified albumin quercetin nanodrug delivery system and its effect on ovarian cancer SKOV3 cells
Objective To prepare dual ligand modified albumin quercetin nanodrug delivery systems(QUE@TAT-PEG-HSANPs),and to observe its effect on ovarian cancer SKOV3 cells.Methods QUE@TAT-PEG-HSANPs was pre-pared,transmission electron microscopy was applied to observe the morphology of nanoparticles.MTT method was applied to detect the cytotoxicity of QUE@TAT-PEG-HSA cells.The uptake of cancer cells and tissue distribution of QUE@TAT-PEG-HSA were observed.Flow cytometry was applied to detect SKOV3 cell apoptosis.An animal model of ovarian cancer transplantation was established,H-E staining was applied to observe the pathological changes of ovarian cancer tissue.TUNEL staining was applied to detect the degree of apoptosis in ovarian cancer tumor cells.Western blot was applied to detect the expression of apoptosis related proteins Caspase-3,Bax,and Bcl-2 in ovarian cancer cells and tissues,and YWHAZ/β-catenin axis related proteins in ovarian cancer tumors.Results QUE@TAT-PEG-HSA nanoparticles are closely arranged,uniform in size,round in shape,smooth in surface and good in dispersion,and their inhibition rate on SKOV3 cells increases in a concentration-dependent manner.The fluorescence intensity of FITC-QUE@TAT-PEG-HSA in SKOV3 cells and ovarian cancer tissues increased gradually over time.The apoptosis rate of SKOV3 cells and expression of Bax and Caspase-3 treated with QUE@TAT-PEG-HSANPs increased,while the expression of Bcl-2 decreased(P＜0.05).The results of tumor transplantation experiment in nude mice showed that QUE,QUE@HSA and QUE@TAT-PEG-HSA treated ovarian cancer tissue cells showed increased necrosis and apoptosis,nucleocytoplasmic concentration and nucleolysis,and increased apop-tosis rate,Bax and Caspase-3 expression.The expressions of Bcl-2,YWHAZ and β-catenin were decreased,and QUE@TAT-PEG-HSA was the most obvious(P＜0.05).Conclusion QUE@TAT-PEG-HSANPs can promote apoptosis of ovarian cancer tissue cells and inhibit tumor growth,and its mechanism of action may be related to the inhibition of the YWHAZ/β-catenin axis.
dual ligand modified albumin quercetin nanodrug delivery systems(QUE@TAT-PEG-HSANPs)ovarian cancerSKOV3 cells
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