Hsieh CCChiu H.-H.Wang C.-H.CHING-HUA KUO2021-06-042021-06-04202016616596https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087409854&doi=10.3390%2fijms21134652&partnerID=40&md5=a71b92c1092cd0f2ecd94c912fa16438https://scholars.lib.ntu.edu.tw/handle/123456789/565170Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.[SDGs]SDG32 oxoisocaproic acid; acetylsalicylic acid; alanine; allantoin; arginine; creatine; interleukin 1beta; interleukin 6; isoleucine; lipopolysaccharide; lysine; methanol; methionine; monocyte chemotactic protein 1; phenylalanine; plasminogen activator inhibitor; tumor necrosis factor; valine; vasculotropin; acetylsalicylic acid; autacoid; plasminogen activator inhibitor 1; adipocyte; amino acid metabolism; animal cell; Article; breast cancer; cancer growth; cancer inhibition; cell growth; cell migration; cell proliferation; cell viability; chemoprophylaxis; controlled study; cytotoxicity; drug efficacy; energy metabolism; enzyme linked immunosorbent assay; fatty acid metabolism; fibroblast; gas chromatography; inflammation; lipid composition; lipogenesis; liquid chromatography-mass spectrometry; mass fragmentography; metabolite; metabolomics; microenvironment; mouse; MTT assay; nonhuman; obesity; oxidative stress; proadipocyte; wound healing assay; 3T3-L1 cell line; adipose tissue; animal; breast; breast tumor; cell differentiation; coculture; conditioned medium; drug effect; female; inflammation; macrophage; metabolism; metabolomics; obesity; pathology; pharmacology; 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Aspirin; Breast; Breast Neoplasms; Cell Differentiation; Cell Proliferation; Chemokine CCL2; Coculture Techniques; Culture Media, Conditioned; Female; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Macrophages; Metabolomics; Mice; Obesity; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alphajournal article10.3390/ijms21134652326299162-s2.0-85087409854