Potential Intervention Mechanisms of Swimming Exercise Against Hepatocellular Carcinoma Cancer Based on Transcriptome Sequencing Technology

XIAO Chulan; YIN Zifei; GUO Bingjie; CHEN Jiaojiao; LI Bai

doi:10.13730/j.issn.2097-2148.2024.03.002

Abstract：Objective To explore the potential mechanism of swimming inhibiting the tumor growth of hepatocellu-lar carcinoma(HCC)in nude mice based on transcriptome sequencing technology.Methods A total of 12 4-week-old BALB/C male nude mice were randomly divided into exercise group and control group,with 6 mice in each.After one week of swimming adaptation,both the nude mice in the exercise group and the control group received subcutaneous tumor inoculation,afterwards,the nude mice in exercise group underwent swimming training(0％body weight load,30 min/d,5 days per week for 4 consecutive weeks).After the training,the nude mice were executed to collect serum and measure tumor weight,at the same time,the cell counting kit 8(CCK-8)test was used to verify the in-hibitory ability of swimming exercise serum on prolifera-tion of HCC cell,and transcriptome sequencing was fur-ther used to explore the potential mechanism of aerobic exercise intervention in HCC.Results The tumor weight of the nude mice in the exercise group significantly decreased compared to the control group[(0.136±0.020)g vs.(0.290±0.099)g,t=26.000,P＜0.05];the CCK-8 test results showed that the optical density(OD)of cells in the ex-ercise group was significantly decreased at 36 h[(0.418±0.001)g vs.(0.431±0.002)g,t=6.000,P＜0.05]and 72 h[(0.402±0.019)g vs.(0.452±0.022)g,t=2.955,P＜0.05]compared to the control group.The results of transcrip-tome sequencing analysis showed that compared with the control group,a total of 1263 differentially expressed genes were screened for sequencing in the exercise group,after intersecting with HCC target genes,a total of 89 intersecting target genes were obtained.The results of protein-protein interaction(PPI)analysis indicated that genes such as signal trans-ducerand activator of transcription 1(STAT1),transporters associated with antigen processing 1(TAP1),recombinant proteasome subunit beta type 9(PSMB9),human leukocyte antigen B(HLA-B),interferon regulatory factor 1(IRF1)and beta-2 microglobulin(β2M)and other genes scored the highest in each algorithm.The results of gene ontology(GO)enrichment analysis showed that there were 20 GO items down-regulated and 13 items up-regulated,among which"nega-tive regulation of canonical Wnt signaling pathway"and other items were closely related to tumors.The enrichment analy-sis results of Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed a total of 11 KEGG items for down-regulated genes,items such as"TNF signaling pathway"and"IL-17 signaling pathway"were closely related to tumors.The results of Gene Set Enrichment Analysis(GSEA)showed that tumor related items included"Prostate canc-er""Pathways in cancer""Leukocyte transendothelial migration"and so on.Conclusion Swimming exercise can inhibit tumor growth of nude mice in HCC model,and its intervention and regulation mechanism may be multifaceted,the Wnt signaling pathway,tumornecrosisfactor(TNF)signaling pathway and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway may all be potential intervention mechanisms.