Experimental Study On Effects Of Wogonin Against Gastric Cancer And Its Regulation Of Dendritic Cell Activities

Gastric cancer is one of malignant tumors with high incidence in China. Currently there are some progress which have been made in research of treatments for gastric cancer, but there is still lacking an effective treatment for unresectable advanced gastric cancer and some patients with relapse after operation. Recently, it has become a hot desire to look for high-efficient and low-toxic anti-gastric cancer drugs in area of traditional Chinese medicine. Extractions from Scutellaria barbata can inhibit tumor growth in a dose-dependent manner, and enhance immune function in our preliminary studies. Therefore, we aimed to observe whether a main active ingredient of Scutellaria barbata, wogonin, can be used as an anti-gastric cancer drug and its molecular mechanisms. This study may provide a new candidate drug for advanced gastric cancer in future.After treated with different concentrations of wogonin, proliferation of SGC-7901cells was determined by a MTT assay, apoptosis rate of SGC-7901cells was detected by flow cytometry. Expression and secretion of VEGF from SGC-7901cells were measured by an immunofluorescence technique and an ELISA assay, respectively. Expression of MICA on SGC-7901cells and activities of dendritic cells induced from peripheral blood mononucleated cells were detected by flow cytometry.The main results are showed as below:1.Wogonin inhibited proliferation of SGC-7901cells:Different concentrations of wogonin (5μg/ml,10μg/ml,20μg/ml,40μg/ml,80p.g/ml,160μg/ml) can effectively inhibit proliferation of SGC-7901cells in a dose and time dependent manner (P<0.05), as compared with the control group of solvent (P<0.05).2.Wogonin induced apoptosis of SGC-7901cells:Apoptosis rate increased with the growing dosage. Apoptosis rates of SGC-7901cells treated with40p.g/ml,160μg/ml of wogonin for24hours in comparison with the solvent control group were statistically significant (P<0.05).3. Wogonin promoted release of reactive oxygen species (ROS) in SGC-7901cells:Intracellular ROS were increased with stimulation of wogonin in the dose dependent manner, as compared with the solvent control group (P<0.05).4. Wogonin stimulated caspase-3activity in SGC-7901cells:Intracellular caspase-3activity were increased with culture of increased dose of wogonin, compared with the solvent control group (P<0.05).5. Wogonin inhibited vascular endothelial cell growth factor (VEGF) secretion of SGC-7901cells:Intracellular VEGF were increased with stimulation of wogonin dose-dependently, but VEGF level in supernatants collected from SGC-7901cell cultures treated with wogonin significantly decreased in the dose-dependent manner(P<0.05).6.Wogonin down-regulated expression of MHC Class I chain-related protein A (MICA) on SGC-7901cells:The expression of MICA was decreased with culture of increased dose of wogonin, compared with the solvent control group (P<0.05).7.Wogonin inhibited maturation of DCs:Wogonin inhibited expression of HLA-DR and CD86molecules on DCs both from gastric cancer patients and healthy individuals (P<0.05). In addition, wogonin can supress LPS-induced DC maturation, and synergize with VEGF to down-regulate DC activities.8.Apoptotic cell debris from SGC-7901cells treated with wogonin were more easier to be phagocytosed by immature dendritic cells (P<0.05).Conclusions:Wogonin has effects of anti-proliferation and apoptosis-promoting on the gastric cancer cell line. The mechanisms may be related with enhanced release of ROS and higher activities of Caspase-3in the SGC-7901cell line. Meanwhile, wogonin inhibits secretion of VEGF and expression MICA in SGC-7901cells. Wogonin down-regulates maturation of DCs induced from peripheral blood mononucleated cells, and immature DCs can efficiently phagocytose apoptotic bodies treated with wogonin.