The Roles And Mechanisms Of Wogonin In Gastric Cancer

Gastric cancer is a common digestive tract malignant tumor,which has a high incidence and mortality in our country.In the occurrence and formation of gastric cancer,various factors are involved,including many molecular pathway abnormalities.Although the incidence of gastric cancer has declined in most parts of the world in recent years,it remains an important factor threatening human health in Eastern Asia and other regions.Currently,the most common therapies for gastric cancer are surgery,chemotherapy and radio therapy.Early gastric cancer has good surgical resection and has a high five-year survival rate.However,early gastric cancer is not easily detected.Surgery is not ideal in the advanced gastric cancer.Therefore,looking for therapeutic drug with high specificity and sensitivity,and less side effects have become the focus of cancer prevention research.Natural medicine has the advantages of less side,biological potency diversity,which attract our attention in antitumor research in recent years.Wogonin,a natural compound which is isolated from Scutellaria baicalensis,has been found to have anti-inflammatory anti-virus,anti-tumor as well as other physiological and pharmacological effects.Studies have shown that wogonin has a good effect in inhibiting gastric cancer.However,the molecular mechanism of wogonin inhibiting gastric cancer is unknown.In this study,we intend to provide new experimental data and theory for clearing the molecular mechanism of wogonin in inhibiting gastric cancer.We first selected three kinds of gastric cancer cells-SGC-7901,BGC-823 and MKN45.Cell viability was studied using CCK8 assays.We found that the viability of gastric cancer cells treated with wogonin was inhibited in a dose-and time-dependent manner.Further study showed that wogonin inhibited colony formation and proliferation in gastric cells.We further established xenograft tumors in nude mice using SGC-7901,and the results showed that wogonin exerted antitumor effects in vivo.Next,analysis of cell cycle showed that wogonin could induce G0/G1 arrest of SGC-7901,but did not affect cell progression in BGC-823.Cell lines treated with wogonin displayed significantly decreased levels of DNA synthesis.Moreover,our results showed that wogonin significantly down-regulated the expression of GO/G1-related proteins including p-RB,CDK6,CDK4 in gastric cancer cells.To explore the molecular mechanisms of wogonin in gastric cancer cells,we analyzed apoptosis by Annexin-V/PI double staining.The result showed that wogonin could induce apoptosis of gastric cancer cells.We also found that wogonin caused a significant decrease of mitochondrial membrane potential in gastric cancer cells by JC-1 staining.In addition,apoptosis-related protein expression such as cleaved PARP and Caspase was upregulated in gastric cancer cells treated with wogonin.The effects of wogonin on cell migration and invasion of GC cells were also investigated.The results showed that wogonin significantly attenuated migration and invasion of GC cells.Wogonin down-regulated the expression of p-STAT3 and p-AKT,and had tumor cell specificity in expression of p-STAT3.Further study showed wogonin down-regulated the expression of JAK.However,transcription level of JAK did not change.Collectively,We found that wogonin inhibited the proliferation,and induced the apoptosis of gastric cancer cells.We also showed that wogonin inhibited invasion and migration of gastric cancer cells.We further found wogonin inhibited the expression of JAK1/2,and down-regulated the activity of JAK/STAT3 pathway of gastric cancer cells.Our work provides new experiment data to explore the effect of wogonin on gastric cancer cells and provided an important theoretical basis for clarifying the molecular mechanism of wogonin in treating gastric cancer,which may be helpful for finding a new therapeutic target for gastric cancer and developing new drugs.