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Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway / 中西医结合学报
Journal of Integrative Medicine ; (12): 418-427, 2021.
Article in English | WPRIM | ID: wpr-888773
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Down-Regulation / Apoptosis / Carcinoma, Hepatocellular / Phosphatidylinositol 3-Kinases / Dynamins / Cell Line, Tumor / Cell Proliferation / Proto-Oncogene Proteins c-akt / Phosphatidylinositol 3-Kinase Limits: Animals Language: English Journal: Journal of Integrative Medicine Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Down-Regulation / Apoptosis / Carcinoma, Hepatocellular / Phosphatidylinositol 3-Kinases / Dynamins / Cell Line, Tumor / Cell Proliferation / Proto-Oncogene Proteins c-akt / Phosphatidylinositol 3-Kinase Limits: Animals Language: English Journal: Journal of Integrative Medicine Year: 2021 Type: Article