Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Pr...Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Previous studies have indicated that ZiyuglycosideⅡ(ZYGⅡ),the major bioactive ingredient extract from Sanguisorba officinalis L.,significantly inhibits the growth of various cancer cells.However,the selective anti-tumor effects of ZYGⅡagainst digestive system cancers are not systemically investigated.In this study,we reported the anti-cancer effect of ZYGⅡon esophageal cancer cells(OE21),cholangiocarcinoma cells(Hu CCT1),gastric cancer cells(BGC-823),liver cancer cells(Hep G2),human colonic cancer cells(HCT116),and pancreatic cancer cells(PANC-1).We also found that ZYGⅡinduced cell cycle arrest,oxidative stress and mitochondrial apoptosis.Network pharmacology analysis suggested that UBC,EGFR and IKBKG are predicted targets of ZYGⅡ.EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYGⅡand both docking simulation and western blot analysis demonstrated that ZYGⅡwas a potential EGFR inhibitor.Furthermore,our results showed synergistic inhibitory effects of ZYGⅡand chemotherapy 5-FU on the growth of cancer cells.In summary,ZYGⅡare effective anti-tumor agents against digestive cancers.Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYGⅡfor the treatment of digestive system cancers.展开更多
基金the grants from Beijing University of Chinese Medicine(Nos.1000041510166 and2020-JYB-ZDGG-038)the National Natural Science Foundation of China(No.81773997)+1 种基金the Shandong Province Key Research Program(2016ZDJS07A21 and 2017CXGC1301)supported by research fund"Traditional Chinese medicine pharmacology and toxicology expert(No.ts201511107)"from Taishan Scholar Project of Shandong Provinceince。
文摘Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Previous studies have indicated that ZiyuglycosideⅡ(ZYGⅡ),the major bioactive ingredient extract from Sanguisorba officinalis L.,significantly inhibits the growth of various cancer cells.However,the selective anti-tumor effects of ZYGⅡagainst digestive system cancers are not systemically investigated.In this study,we reported the anti-cancer effect of ZYGⅡon esophageal cancer cells(OE21),cholangiocarcinoma cells(Hu CCT1),gastric cancer cells(BGC-823),liver cancer cells(Hep G2),human colonic cancer cells(HCT116),and pancreatic cancer cells(PANC-1).We also found that ZYGⅡinduced cell cycle arrest,oxidative stress and mitochondrial apoptosis.Network pharmacology analysis suggested that UBC,EGFR and IKBKG are predicted targets of ZYGⅡ.EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYGⅡand both docking simulation and western blot analysis demonstrated that ZYGⅡwas a potential EGFR inhibitor.Furthermore,our results showed synergistic inhibitory effects of ZYGⅡand chemotherapy 5-FU on the growth of cancer cells.In summary,ZYGⅡare effective anti-tumor agents against digestive cancers.Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYGⅡfor the treatment of digestive system cancers.