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.

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.