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Aerobic exercise preconditioning suppresses subcutaneous tumorigenesis via PI3K/AKT-driven metabolic epigenetic reprogramming and immune microenvironment remodeling

  • 0School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China; School of Physical Education and Health, East China Normal University, Shanghai 200241, China; School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
Experimental Gerontology +

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July 13, 2025

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July 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Aerobic exercise preconditioning inhibits subcutaneous tumor growth by downregulating glucose metabolism genes and reducing M1 macrophage infiltration. This antitumor effect is linked to epigenetic reprogramming via the PI3K/AKT pathway.

Area Of Science

  • Oncology
  • Exercise Physiology
  • Molecular Biology

Background

  • Aerobic exercise is known to inhibit tumors, with aerobic glycolysis linked to tumor development.
  • The effect of exercise preconditioning on subcutaneous tumor growth and its underlying mechanisms require further investigation.

Purpose Of The Study

  • To investigate the impact of aerobic exercise preconditioning on subcutaneous tumor growth in mice.
  • To elucidate the molecular mechanisms by which exercise influences tumor metabolism and growth.

Main Methods

  • Mice were subjected to 12 weeks of aerobic exercise before subcutaneous transplantation of Hepa1-6 cells.
  • Gene expression analysis (RNA-Seq), Western blot, immunofluorescence, and DNA methylation analysis were performed on tumor tissues.
  • Analysis included assessment of glucose metabolism markers (PKM2, GLUT1, LDHA, HK2), PI3K/AKT pathway activation, immune cell infiltration, and epigenetic modifications.

Main Results

  • Aerobic preconditioning significantly inhibited Hepa1-6 tumor growth compared to controls.
  • Exercise reduced the expression of key glucose metabolism genes and downregulated PI3K/AKT pathway proteins (P-PI3K, P-AKT).
  • Exercise decreased M1 macrophage infiltration and was associated with liver DNA methylation changes in the PI3K/Akt pathway in HCC models.

Conclusions

  • Aerobic exercise preconditioning exerts antitumor effects by epigenetically reprogramming tumor metabolism, primarily through the PI3K/AKT pathway.
  • Exercise-induced inhibition of tumor growth involves downregulation of glucose metabolism and modulation of the tumor immune microenvironment.
  • The PI3K/AKT pathway serves as a central mediator in exercise's regulation of tumor metabolism and growth.

Keywords:

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