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Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex

Science Bulletin 2022年第8期67卷 813-824,M0003页

作者： Yajun Geng Shili Chen Yang Yang Huijie Miao Xuechuan Li Guoqiang Li Jian Ma TongZhang 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 BoChen 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 HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of Biliary Tract Disease Research Shanghai 200127China Department of Hepatobiliary Surgery Affiliated Hospital of Jining Medical UniversityJining 272129China Department of General Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010050China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Hepatobiliary and Pancreatic Surgery Henan Provincial People’s HospitalZhengzhou 450003China Department of Surgical Oncology First Affiliated Hospital of Bengbu Medical CollegeBengbu 233099China Department of General Surgery Changshu No.1 People’s Hospital Affiliated to Soochow UniversityChangshu 215500China Department of Biliary Surgery Eastern Hepatobiliary Surgery HospitalShanghai 200433China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Hepatobiliary Surgery Affiliated Hospital of Nantong UniversityNantong 226001China State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology Shanghai Cancer InstituteShanghai 200127China Department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai 200127China

Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various *** 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 relationship between long-term exposure to soy isoflavones and the occurrence and progression of *** case-control study(n=85 pairs)found that the high level of plasma soy isoflavoneDgenistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/m L compared to≤19.30ng/m L,crude odds ratio 0.15,95%CI 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 proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in *** long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3βaxis,leading to downregulation of the MCM complex in GBC *** 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.

关键词： Gallbladder cancer Dietary exposure Genistein ERBB2 pathway activation MCM protein complex

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