Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer(GBC),therefore,it is important to investigate the rela-tionship between long-term exposure to soy isoflavones and the occurrence and progression of GBC.This case-control study(n=85 pairs)found that the high level of plasma soy isoflavone-genistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/mL compared to≤19.30 ng/mL,crude odds ratio 0.15,95％Cl 0.04-0.59;P for trend=0.016),and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue(n=85).Consistent with these results,the pro-liferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo.The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3β axis,leading to downregulation of the MCM complex in GBC cells.In summary,long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.

Yajun Geng;Shili Chen;Yang Yang;Huijie Miao;Xuechuan Li;Guoqiang Li;Jian Ma;Tong Zhang;Tai Ren;Yongsheng Li;Lin Li;Liguo Liu;Jiahua Yang;Ziyi Wang;Lu Zou;Ke Liu;Yang Li;Siyuan Yan;Xuya Cui;Xuheng Sun;Bo Yang;Lingxiao Zhang;Xusheng Han;Chuanlei Wang;Bo Chen;Xueliang Yue;Wei Liang;Jianjun Ren;Jianguang Jia;Jianfeng Gu;Zhizhen Li;Tiansuo Zhao;Peng Wang;Dong Wei;Shimei Qiu;Dongxi Xiang;Xinsen Xu;Wei Chen;Min He;Linhua Yang;Hui Wang;Tao Chen;Rong Hua;Xu'an Wang;Xiangsong Wu;Wei Gong;Guangyi Wang;Maolan Li;Wei Zhang;Rong Shao;Wenguang Wu;Yingbin Liu

Department of Biliary-Pancreatic Surgery,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of General Surgery,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Shanghai Key Laboratory of Biliary Tract Disease Research,Shanghai 200127,China;Department of Hepatobiliary Surgery,Affiliated Hospital of Jining Medical University,Jining 272129,China;Department of General Surgery,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China;Department of Hepatobiliary and Pancreatic Surgery,The First Hospital of Jilin University,Changchun 130021,China;Department of Hepatobiliary and Pancreatic Surgery,Henan Provincial People's Hospital,Zhengzhou 450003,China;Department of Surgical Oncology,First Affiliated Hospital of Bengbu Medical College,Bengbu 233099,China;Department of General Surgery,Changshu No.1 People's Hospital Affiliated to Soochow University,Changshu 215500,China;Department of Biliary Surgery,Eastern Hepatobiliary Surgery Hospital,Shanghai 200433,China;Department of Pancreatic Cancer,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China;Department of Hepatobiliary Surgery,Affiliated Hospital of Nantong University,Nantong 226001,China;State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology,Shanghai Cancer Institute,Shanghai 200127,China;Department of Pharmacology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Shanghai 200127,China

科学通报（英文版）

[1]Yajun Geng;Shili Chen;Yang Yang;Huijie Miao;Xuechuan Li;Guoqiang Li;Jian Ma;Tong Zhang;Tai Ren;Yongsheng Li;Lin Li;Liguo Liu;Jiahua Yang;Ziyi Wang;Lu Zou;Ke Liu;Yang Li;Siyuan Yan;Xuya Cui;Xuheng Sun;Bo Yang;Lingxiao Zhang;Xusheng Han;Chuanlei Wang;Bo Chen;Xueliang Yue;Wei Liang;Jianjun Ren;Jianguang Jia;Jianfeng Gu;Zhizhen Li;Tiansuo Zhao;Peng Wang;Dong Wei;Shimei Qiu;Dongxi Xiang;Xinsen Xu;Wei Chen;Min He;Linhua Yang;Hui Wang;Tao Chen;Rong Hua;Xu'an Wang;Xiangsong Wu;Wei Gong;Guangyi Wang;Maolan Li;Wei Zhang;Rong Shao;Wenguang Wu;Yingbin Liu-.Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex)[J].科学通报（英文版）,2022(08):813-824

PTK6

Long,term,exposure,genistein,inhibits,proliferation,gallbladder,cancer,by,downregulating,MCM,complex,Soy,isoflavones,natural,tyrosine,inhibitors,closely,associated,decreased,morbidity,mortality,various,tumors,activation,kinases,such,ERBB2,mechanism,which,cholecystitis,transforms,into,GBC,therefore,important,investigate,tionship,between,long,soy,occurrence,progression,This,case,control,study,pairs,found,that,high,level,plasma,GEN,was,lower,risk,compared,crude,odds,Cl,trend,negatively,correlated,Ki67,expression,tissue,Consistent,these,results,cells,inhibited,models,vitro,vivo,reduced,activity,impaired,function,AKT,GSK3,axis,leading,downregulation,In,summary,products,intake,might,play,certain,role,preventing,inhibiting

0.517651