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 cholecystit...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 relationship 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 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 vivo.The 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 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.展开更多
基金supported by the National Natural Science Foundation of China(2019XH004,81874181,82073206,21705108,and 81773043)the Emerging Frontier Program of Hospital Development Centre(SHDC12018107)+4 种基金the Key Program of Shanghai Science and Technology Commission(YDZX20193100004049)the State Key Laboratory of Oncogenes and Related Genes(KF2120)the National Key Research and Development Program of China(2021YFE0203300)the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG14)he Program of Shanghai Academic Research Leader(19XD1422700)。
文摘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 relationship 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 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 vivo.The 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 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.
