期刊
CANCER LETTERS
卷 543, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2022.215793
关键词
CTR1; Glucose restriction; AMPK; ROS; NSCLC
类别
资金
- Priority Academic Program Development of Jiangsu Higher Education Institutions, China
Glucose restriction induces ROS-AMPK-mediated CTR1 expression in NSCLC cells. Feeding a low-carbohydrate ketogenic diet in combination with cisplatin enhances the efficacy of cisplatin and increases survival in a mouse model.
Cisplatin is one of the principal platinum-based chemotherapeutic agents for many types of cancer, including non-small-cell lung cancer (NSCLC). Copper transporter 1 (CTR1) plays a significant role in increasing cellular cisplatin uptake and sensitivity. The current study found that glucose restriction upregulated AMPK (AMP-activated protein kinase) through reactive oxygen species (ROS) to induce CTR1 expression in NSCLC cells. Direct upregulation of ROS levels also activated AMPK expression. The changes in CTR1 expression were consistent with glucose concentrations and AMPK expression. Feeding a low-carbohydrate ketogenic diet (a glucose restriction diet) to a severe combined immune deficiency (SCID) mouse xenograft model significantly enhanced the efficacy of cisplatin. The tumor size was significantly smaller in the group treated with cisplatin plus the low-carbohydrate ketogenic diet than in the group treated with cisplatin alone. Survival was longer in mice treated with the low-carbohydrate ketogenic diet than in the controls. Mice fed the low-carbohydrate ketogenic diet showed increased expression of CTR1 and AMPK in tumor tissues. These results suggest a novel mechanism whereby glucose restriction induces ROS-AMPK-mediated CTR1 expression in NSCLC, indicating glucose restriction as an effective adjuvant NSCLC therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据