Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism
Shi D, Fang G, Chen Q, Li J, Ruan X, Lian X
BMC medicine · 31 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Chongqing Postdoctoral Science Foundation
- Government
- National Natural Science Foundation of China
- Government
- China Postdoctoral Science Foundation
- University or hospital
- Chongqing Medical University
- Government
- Chongqing Municipal Education Commission
- Nonprofit
- Postdoctoral Research Foundation of China
- Unclassified
- Young Scientists Fund
- Grants
- Postdoctoral Research Foundation of China (2021M693755); National Natural Science Foundation of China (8210120502); National Natural Science Foundation of China (81973030); Chongqing Postdoctoral Science Foundation ([2020] 379); Chongqing Medical University (W0085); Young Scientists Fund (8210120502)
Based on 7 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2023-11-03 · BMC Med · vol. 21 · issue 1 · p. 417
- Publisher
- BioMed Central
- Cited
- 40 citations · more than 97% of similar papers · 5.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 61 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Dietary Effects on Health · Circadian rhythm and melatonin · Epigenetics and DNA Methylation
- Keywords
- Downregulation and upregulation, Lung cancer, Circadian rhythm, Gene knockdown, Tumor progression, Cancer research, Medicine, Cancer, Autophagy, Cancer cell, Oncogene, Internal medicine, Biology, Cell cycle, Cell culture, Gene, Apoptosis, Biochemistry
- MeSH
- lung, animals, humans, mice, lung neoplasms, disease models, animal, circadian rhythm, intermittent fasting
6 authors
From CN
- Dan Shi · correspondingDalian Medical University; Second Affiliated Hospital of Chongqing Medical University; Chongqing Public Health Medical Center; Chongqing Medical University
- Gaofeng FangChongqing Public Health Medical Center; Chongqing Medical University
- Qianyao ChenChongqing Public Health Medical Center; Chongqing Medical University
- Jianling LiChongqing Public Health Medical Center; Chongqing Medical University
- Xiongzhong Ruan · correspondingDalian Medical University; Second Affiliated Hospital of Chongqing Medical University; Chongqing Medical University
- Xuemei Lian · correspondingDalian Medical University; Second Affiliated Hospital of Chongqing Medical University; Chongqing Public Health Medical Center; Chongqing Medical University
Abstract
Background
Accumulating 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.
Methods
This 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.
Results
We 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.
Conclusions
Six-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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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