ABSTRACT: Previous research reports have shown that curcumin and exercise have good anti-tumor effects. However, there is currently a lack of relevant research reports on the combined effect of physical exercise with curcumin supplementation on cancer and its mechanisms. This study constructed an anti breast tumor mouse model under the combined effects of curcumin treatment and swimming exercise. Transcriptomics and metabolomics techniques were used to screen differentially expressed genes and metabolites, evaluate the anti-cancer effect, and analyze the molecular regulatory mechanisms related to metabolism. Through the mouse phenotype observation, including the detection of tumor appearance, tumor imaging in vivo, and HE staining results of pathological sections, curcumin administration and exercise intervention combined treatment has more obvious inhibitory effect on breast cancer than a single treatment. The combined effect treatment group had a total of 445 differentially expressed genes, including 154 upregulated genes and 291 downregulated genes; Functional enrichment analysis showed that calcium signaling pathway, Wnt signaling pathway, PI3K Akt signaling pathway and IL-17 signaling pathway significantly participated in the anti breast cancer process of curcumin combined exercise. The results of inter group differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways: amino sugar and nucleotide sugar metabolism, as well as amino acid biosynthesis. The metabolic pathways of amino sugars and nucleotide sugars include chitosan, D-glucosamine 6-phosphate, L-fucose, and N-acetyl beta-mannosamine; The biosynthetic pathway of amino acids includes DL isoleucine, DL tyrosine, and homocysteine. Finally, through the joint analysis of transcriptome and metabolomic data, it was found that the most significantly correlated genes among the positive ion mode differential metabolites under the combined exercise of curcumin were catechins, including 8 correlated genes Cpeb2, Grem1, Nid1, Samd5, Hsph1, Glis3, Mapk6, and Phldb2; The most significant negative ion mode differential metabolite is 1-myristyl-2-hydroxy-sn-glycerol-3-phosphate ethanolamine, which includes 27 correlated genes Mmp10, Dock4, Dpysl3, Tnfsfm13, Etf1, Dzip1, Scara5, Plcg2, Dusp18, Zmat3, Marf1, Tox4, Tmem119, Tep1, Cybc1, AW549877, Dynap, Hhip, Tpm3, Zc3hav1l, Sema5a, Txlng, Lrrc55, Pprrx1, Rtl8b, Adam19, and Frrs1.
