Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway.

Abstract

OBJECTIVE:

Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis.

METHODS:

Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise.

RESULTS:

The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor.

CONCLUSION:

Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.

• Authors: Tong Zhao, Bing-Jie Guo, Chu-Lan Xiao, Jiao-Jiao Chen, Can Lü, Fan-Fu Fang, Bai Li
• Journal: Journal of integrative medicine (J Integr Med) Vol. 19 Issue 5 Pg. 418-427 (09 2021) ISSN: 2095-4964 [Print] Netherlands
• PMID: 34454893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Chemical References

• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Dnm1l protein, mouse
• Dynamins

Topics

• Animals
• Apoptosis
• Carcinoma, Hepatocellular (genetics, therapy)
• Cell Line, Tumor
• Cell Proliferation
• Down-Regulation
• Dynamins
• Liver Neoplasms (genetics, therapy)
• Mice
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction