Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism

作者全名："Shi, Dan; Fang, Gaofeng; Chen, Qianyao; Li, Jianling; Ruan, Xiongzhong; Lian, Xuemei"

作者地址："[Shi, Dan; Fang, Gaofeng; Chen, Qianyao; Li, Jianling; Ruan, Xiongzhong; Lian, Xuemei] Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Key Lab Mol Biol Infect Dis,Minist Educ, Chongqing 400016, Peoples R China; [Shi, Dan; Fang, Gaofeng; Chen, Qianyao; Li, Jianling; Lian, Xuemei] Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing 400016, Peoples R China; [Shi, Dan] Chongqing Med Univ, Res Ctr Environm & Populat Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Shi, Dan] Chongqing Med Univ, Sch Publ Hlth, Nutr Innovat Platform Sichuan & Chongqing, Chongqing, Peoples R China"

通信作者："Shi, D; Ruan, XZ; Lian, XM (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Key Lab Mol Biol Infect Dis,Minist Educ, Chongqing 400016, Peoples R China.; Shi, D; Lian, XM (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing 400016, Peoples R China.; Shi, D (通讯作者)，Chongqing Med Univ, Res Ctr Environm & Populat Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China.; Shi, D (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Nutr Innovat Platform Sichuan & Chongqing, Chongqing, Peoples R China."

来源：BMC MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001093169900001

JCR分区：Q1

影响因子：7

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Time-restricted feeding; Lung cancer; Progression; Circadian rhythm; TIM; Autophagy

摘要："BackgroundAccumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression.MethodsThis study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux.ResultsWe found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model.ConclusionsSix-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy."

基金机构：We would like to thank Dr. Chong Zhong for the assistance in pathology examinations and quantification. We would like to thank professor Xiaoqiu Xiao for the advice in the experimental design. We would like to thank Applied Protein Technology company for t

基金资助正文：We would like to thank Dr. Chong Zhong for the assistance in pathology examinations and quantification. We would like to thank professor Xiaoqiu Xiao for the advice in the experimental design. We would like to thank Applied Protein Technology company for the support in targeted metabolomics detection and analysis. We would like to thank professor Lin Yong for providing the mCherry-GFP-LC3 plasmid used in this study. We would like to thank the staff from electron microscope laboratory of Chongqing Medical University for the help with transmission electron microscope experiment. We are also indebted to Dan Yang for her advice in rhythmic experiments and the writing assistance from American Journal Experts.