Study On The Anti-tumor Mechanism Of Wogonin With Gene-chip Technology

Previous studies have demonstrated that wogonin, a botanical monoflavonoid extracted from the root of Scutellaria baicalensi Georgi, could inhibit cell growth in various tumors and is a very promising and potential antitumor drugs with mutiple targets. However, the underlying mechanisms of wogonin’ anti-tumor effect still remain.elusive Here we found that wogonin at the doses of (12.5～200μmol/L) effectively inhibited the proliferation of hepatoma carcinoma cell HepG2, but had no significant inhibition on the growth of gastric carcinoma cell SGC-7901and hepatoma carcinoma cell Huh7.The IC50of wogonin for HepG2was115.7μmol/L. Flow cytometry was used to analyze the cell cycle distribution and apoptosis rate. The results showed that wogonin induced the apoptosis of cell by blocking cell at G1phase and inhibiting DNA synthesis in S phase. The apoptotic rate of wogonin treating HepG2for48h with the concentration of0,50,100,200μmol/L is2.58±0.07%,4.04±0.15%,9.54±0.14%and27.33±0.12%respectively. Results of scratch test and cell migration assay indicated that wogonin (50～200μmol/L) inhibited the mobility of HepG2. All of these results demonstrated that wogonin showed significant anticancer effects. The whole genome oligonucleotide microarray (Affymetrix HG-u133Plus2.0) was applied to evaluate the gene expression profile of hepatocellular cancer cells after wogonin treatment for48hours. A total of406differentially expressed genes were observed, among which,295were up-regulated, and the other111were down-regulated. In six comparison studies, there were12genes which were up-regulated more than4times, such as FAM129A, INHBE, GDF15, etc. In addition, there were8genes which were down-regulated more than4times, such as Cox1, H19, etc. These differentially expressed genes are mainly involved in148functional categories by Gene Ontology(GO) and61pathways of the genes by KEGG, including apoptosis, tumorogenesis, metabolism, signal transduction, cell cycle and material transportation. Among these pathways, cell cycle and MAPK pathway were most affected. Cell cyclerelated genes GADD45alpha, CDKN1A and CDKN2B were up-regulated, MAPK pathway-related gene MAP4K4was up-regulated, and ARPB1, JUN, EGFR, MAP2K7genes, tumor metastasis-related gene NDRG1were down-regulated. These differentially expressed genes may be the targets of wogonin. In conclusion, the present study sheds new light on the molecular mechanism of the anti-tumor effect of wogonin.