医科院肿瘤医院:高脂饮食通过抑制铁死亡,恶化结肠炎相关肿瘤发生
创作:aluba 审核:aluba 2021年11月08日
  • 在AOM/DSS诱导的结肠炎相关结直肠癌(CAC)小鼠模型中,铁、脂质过氧化、铁死亡标志物升高;
  • 铁死亡抑制剂(ferrostatin-1)可增加CAC小鼠的结肠肿瘤负荷;
  • 高脂饮食抑制脂质过氧化,并降低铁死亡标志物表达,以增加CAC小鼠的结肠肿瘤数量;
  • 铁死亡标志物的表达与CAC小鼠的肿瘤数量呈负相关;
  • 可阻断铁死亡的脂质混合物通过负向调节CHAC1(内质网应激信号)抑制谷胱甘肽的降解;
  • 铁死亡诱导剂可部分抑制高脂饮食对CAC小鼠的促肿瘤作用。
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aluba
中国医学科学院肿瘤医院的汪红英团队在Free Radical Biology and Medicine上发表的一项最新研究结果,发现高脂饮食可通过抑制内质网应激通路介导的肿瘤细胞的铁死亡,从而恶化AOM/DSS诱导的小鼠结肠炎相关结直肠癌。
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High-fat diet aggravates colitis-associated carcinogenesis by evading ferroptosis in the ER stress-mediated pathway

高脂饮食通过逃避内质网应激通路介导的铁死亡,以恶化结肠炎相关肿瘤发生

10.1016/j.freeradbiomed.2021.10.022

2021-10-21, Article

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Ferroptosis, a type of programmed cell death caused by lipid peroxidation has recently been observed in colitis. Whether a high-fat diet (HFD) affects ferroptosis and whether it contributes to colitis-associated carcinogenesis (CAC) has not been explored. We found iron, lipid peroxidation, and ferroptotic markers to be elevated in AOM/DSS (azoxymethane/dextran sulfate sodium)-induced mouse CAC model. Transmission electron microscopy also confirmed the occurrence of ferroptosis in colonic tissues. Treatment with the ferroptosis inhibitor, ferrostatin-1 increased the incidence of CAC. Compared with iso-caloric control mice, HFD mice exhibited increased tumor number and a higher degree of dysplasia following repression of lipid peroxidation and ferroptosis marker expression in mouse colon tissue. Furthermore, ferroptosis markers were negatively correlated with the tumor number in mice. In vitro, a lipid mixture blocked ferroptosis in various colorectal cancer cell lines and inhibited GSH degradation by negatively regulating CHAC1, a target in ER stress signaling. Finally, the ferroptosis inducer partly abolished the pro-tumor effect of the HFD on CAC in vivo. Collectively, these findings suggest that a HFD aggravates CAC through the evasion of ferroptosis in the ER stress-mediated pathway and provides a new perspective for CAC prevention in the future.

First Authors:
Xiaoli Zhang

Correspondence Authors:
Hongying Wang

All Authors:
Xiaoli Zhang,Weiwei Li,Yiming Ma,Xinhua Zhao,Longmei He,Peng Sun,Hongying Wang

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