Study On The Anti-Gastric Cancer Activity And Molecular Mechanism Of The Total Saponins From Tupistra Chinensis Baker

Aim:The high morbidity and mortality rate of gastric cancer is one of the most common malignant tumors in the world.Tupistra chinensis Baker（syn.Rohdea chinensis）is a folk medicine mainly distributed in China,and steroidal saponins are its main antitumor ingredients.The total steroidal saponins of T.chinensis（TCS）exhibited potent anti-proliferative activity in gastric cancer cells in our former study,but the molecular mechanism of TCS remains to be revealed.In the present study,we studied the potential anti-proliferative activity and anti-tumor mechanism of TCS on gastric cancer in vitro and in vivo.Methods:In vitro,MTT assay was used to detect the proliferative ability of TCS on five gastric cancer cell lines（SGC-7901,AGS,MGC-803,BGS-823,KATO-iii）.Wound assay and Transwell assay were used to detect the effect of TCS on the migration ability of gastric cancer cells.Flow cytometry was performed to analyze cell apoptosis,cell cycle,mitochondrial membrane potential and reactive oxygen species expression level.Western blot was used to detect the expression of cycle,apoptosis,autophagy and other related proteins,and the role of p53 protein in TCS-induced apoptosis of AGS cells was detected by cell transfection.In vivo,a xenograft model was established by injecting SGC-7901 cells into nude mice.Result:In vitro,TCS inhibited the proliferation of five kinds of gastric cancer cells.The inhibition of SGC-7901 and AGS cells was achieved by inducing G₂/M phase arrest.Further studies showed that TCS induced SGC-7901 cells apoptosis through ROS mediated PI3K/Akt/m TOR signaling pathway,and AGS cells apoptosis through p53 mediated pathway.In addition,we found that TCS induced protective autophagy in both gastric cancer cells.Finally,it was found that TCS significantly inhibited the migration ability of SGC-7901 cells and AGS cells.In vivo,the results showed that TCS inhibited the growth of SGC-7901 xenografts in nude mice.Conclusion:These results indicated that TCS exhibited significant anti-gastric cancer activity in vivo and in vitro,which provides a new idea for the research and development of TCS as a new anti-gastric cancer drug.