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In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin
Xiangming Ma1,2, Fei Tian3, Jian Li4
1Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, Hebei, China.
Abstract:
Ketogenic diet (KD) may benefit patients with liver cancer, but the underlying mechanism of its anti-cancer effect remains an open issue. This work aimed to explore the influence of simulated KD on the proliferation and migration of cultured hepatoma cells. The low-glucose medium supplemented with β-hydroxybutyrate (BHB-Glow) was utilized to simulate clinical KD treatment. Western blot was utilized for detecting the expression of glycolysis-related proteins, Seahorse XF96 for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), and ELISA for insulin content. Expression of FOXC2 in liver cancer cells was analyzed by bioinformatics and qPCR. Cell Count Kit-8 (CCK-8) testing kit was utilized for testing cell viability. KD treatment significantly reduced the expression of glycolysis-related proteins in Huh-7 cells, inhibited insulin production in β islet cells, reduced ECAR, and increased OCR. FOXC2 was significantly up-regulated in Huh-7 cell line, and sh-FOXC2 hindered the proliferation and migration of Huh-7 cells. The exogenous addition of insulin promoted the malignant progression of Huh-7 cells. Together, the medium simulating KD environment strengthened the protection of liver cancer cells by reducing insulin production and down-regulating FOXC2 expression. This study confirmed through in vitro cell experiments that KD could inhibit the proliferation and migration of liver cancer cells by targeting down regulation of insulin and FOXC2 expression, providing new theoretical basis for the treatment of liver cancer patients.
Insights
The ketogenic diet (KD) inhibits liver cancer cell growth by reducing insulin production and down-regulating FOXC2 expression. This study provides new insights into KD
Area of Science:
- Oncology
- Metabolic Research
- Hepatology
Background:
- The ketogenic diet (KD) shows potential benefits for liver cancer patients.
- The precise mechanisms behind KD's anti-cancer effects in liver cancer are not fully understood.
Purpose of the Study:
- To investigate the impact of a simulated ketogenic diet on hepatoma cell proliferation and migration.
- To elucidate the molecular pathways involved in KD's anti-cancer activity in liver cancer.
Main Methods:
- Simulated KD using β-hydroxybutyrate (BHB-Glow) in low-glucose medium.
- Western blot, Seahorse XF96 analysis (OCR/ECAR), ELISA, bioinformatics, qPCR, and CCK-8 assay were employed.
- FOXC2 expression and its role in cell proliferation and migration were assessed.
Main Results:
- KD simulation reduced glycolysis-related proteins, extracellular acidification rate (ECAR), and insulin production.
- KD simulation increased oxygen consumption rate (OCR) and significantly up-regulated FOXC2 expression in Huh-7 cells.
- FOXC2 knockdown (sh-FOXC2) inhibited proliferation and migration; exogenous insulin promoted malignant progression.
Conclusions:
- Ketogenic diet inhibits liver cancer cell proliferation and migration by reducing insulin production and down-regulating FOXC2 expression.
- This study offers a novel theoretical basis for utilizing KD in liver cancer treatment.
- In vitro findings highlight the interplay between metabolism, insulin, and FOXC2 in liver cancer progression.
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