The Research Of VEGF SiVEGF Interference In Hepatocellular Carcinoma Based On A Biodegradable Nanocarrier

ObjectiveTo research the effects and mechanism of PEG-SS-PLL/siVEGF preparedbased on a biodegradable nanocarrier in hepatocellular carcinoma both in vitroand in vivo.MethodsLoad VEGF siVEGF and synthesize PEG-SS-PLL/siVEGF using abiodegradable nanocarrier PEG-SS-PLL.HepG2cell culture and establish HepG2-derived tumor model in nudemice.In vitro, the siVEGF transfection efficiency was assayed usingfluorescence microscope, the cytotoxicity of PEG-SS-PLL/siVEGF complexwas evaluated by MTT method, apoptosis rates were investigated by FCM（flow cytometry） between experimental groups and BLANK group In vivo,The tumor growth curves and tumor-suppressing rates were observed betweenexperimental groups and control group.VEGF mRNA and protein levels were determined by RT-PCR analysisand Western blot using samples taken from HepG2cells and the tumortissues. The VEGF protein levels were also investigated byimmunohistochemistry analysis. Resultsthe PEG-SS-PLL/siVEGF showed largely enhanced siVEGF transfectionactivity and lower cytotoxicity in vitro, and the apoptosis rate was much higherthan BLANK group. After administration, the VEGF mRNA and protein levelsin HepG2cells were decreased significantly.In vivo experiments, we found that PEG-SS-PLL/siVEGF couldsignificantly suppress the growth of tumor by50.12%, and after treatment, theVEGF mRNA and protein levels of tumor tissues were decreased significantly.in EG-SS-PLL/siVEGF.ConclusionPEG-SS-PLL/VEGF siVEGF were not cytotoxic and were able totransfect HepG2cells in vitro. Treatment with PEG-SS-PLL/VEGF siVEGFcould induce HepG2cells apoptosis in vitro and inhibit tumor growth in aHepG2-derived tumor model in nude mice.The administration of VEGF siVEGF dramatically reduced VEGF mRNAand protein expression both in vitro and in vivo, suggesting that the mechanismanti-tumor activity of VEGF siVEGF may include anti-angiogenesis.