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Updated: Mar 6, 2026
The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury
Published on: October 21, 2017
Dietary restriction protects against diethylnitrosamine-induced hepatocellular tumorigenesis by restoring the
Ting Duan1, Wenjie Sun1, Mohan Zhang1
1Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
Abstract:
Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent malignancies, worse still, there are very limited therapeutic measures with poor clinical outcomes. Dietary restriction (DR) has been known to inhibit spontaneous and induced tumors in several species, but the mechanisms are little known. In the current study, by using a diethylnitrosamine (DEN)-induced HCC mice model, we found that DR significantly reduced the hepatic tumor number and size, delayed tumor development, suppressed proliferation and promoted apoptosis. Further transcriptome sequencing of liver tissues from the DEN and the DEN accompanied with DR (DEN+DR) mice showed that DEN induced profound changes in the gene expression profile, especially in cancer-related pathways while DR treatment reversed most of the disturbed gene expression induced by DEN. Finally, transcription factor enrichment analysis uncovered the transcription factor specificity protein 1 (SP1) probably functioned as the main regulator of gene changes, orchestrating the protective effects of DR on DEN induced HCC. Taken together, by the first comprehensive transcriptome analysis, we elucidate that DR protects aginst DEN-induced HCC by restoring the disturbed gene expression profile, which holds the promise to provide effective molecular targets for cancer therapies.
Insights
Dietary restriction (DR) significantly reduces hepatocellular carcinoma (HCC) development in mice by reversing gene expression changes. This approach offers potential new molecular targets for liver cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Hepatocellular carcinoma (HCC) is a lethal malignancy with limited effective treatments.
- Dietary restriction (DR) shows promise in inhibiting tumors, but its mechanisms remain unclear.
Purpose of the Study:
- To investigate the protective mechanisms of dietary restriction (DR) against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in a mouse model.
- To elucidate the molecular pathways modulated by DR in HCC development.
Main Methods:
- Utilized a diethylnitrosamine (DEN)-induced HCC mouse model.
- Performed transcriptome sequencing on liver tissues from DEN-exposed and DR-treated mice.
- Conducted transcription factor enrichment analysis.
Main Results:
- DR significantly reduced tumor number, size, and delayed development in the HCC mouse model.
- DR suppressed cancer cell proliferation and promoted apoptosis.
- Transcriptome analysis revealed DR reversed most DEN-induced gene expression changes, particularly in cancer-related pathways.
- Specificity protein 1 (SP1) was identified as a key regulator of DR's protective effects.
Conclusions:
- Dietary restriction (DR) demonstrates significant protective effects against diethylnitrosamine-induced hepatocellular carcinoma (HCC) in mice.
- DR functions by restoring disturbed gene expression profiles, highlighting its therapeutic potential.
- The findings identify SP1 as a crucial regulator and suggest potential molecular targets for HCC therapy.
