Exercise Inhibits Hcc Tumor Growthand Modulates Lipid Metabolism Reprogramming In Tme And Downregulates Ampk Pathway

PURPOSE: To examine the impact of exercise intervention on hepatocellular carcinoma and its metabolic processes. METHODS: Male C57BL/6 mice were randomly assigned to either a sedentary group (Sed) or an exercise group (Ex). After a period of 6 weeks, all mice were subcutaneously inoculated with Hepa1-6 cells on their right back. The exercise group (Ex) continued their exercise regimen for an additional 4 weeks in order to observe tumor growth in vivo. Mouse tumor tissues were subjected to LC-MS non-target metabolome sequencing. The expression of FASN was assessed in both tumor and adjacent tissues of hepatocellular carcinoma patients. Furthermore, the expressions of FASN, CPT1, CD36, and Ki67 were measured. Finally, the triglyceride content in mouse tumor tissue was determined. RESULTS: The tumor inhibition rate in the Ex group (475.23 ± 22.16) exhibited a 20% decrease compared to the Sed group (590.59 ± 54.29), and there was a decrease in the expression of Ki67 (0.67 ± 0.075; 1.22 ± 0.068; P < 0.05). KEGG enrichment analysis of different metabolites in the Ex group and Sed group revealed that the AMPK signaling pathway enrichment was the most significant (P < 0.01). ADP was significantly up-regulated in the Ex group (136.64 ± 3.95; 79.13 ± 49.03; P < 0.05), while AICAR was significantly down-regulated (164.59 ± 48.13; 254.69 ± 12.32; P < 0.05). The expression of FASN in clinical tumor samples (222.7 ± 16.46) was significantly higher compared to that in para-cancer liver tissues (165.2 ± 11.85) (P < 0.05). Additionally, in the 102.975 ± 12.97 group, the expressions of FASN, CPT1, and CD36 were significantly higher than those in the Sed group (350.276 ± 3.75; 24.807 ± 3.42; 183.789 ± 17.18) (P < 0.05). Moreover, there was a noticeable increase in the accumulation of lipid droplets in tumor cells. CONCLUSIONS: Exercise has the potential to further restrict the energy supply of tumor cells through the inhibition of fatty acid uptake, oxidative degradation, and de novo synthesis.