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