Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited. Therefore, the purpose of the present study was to investigate the mechanisms by which aspirin prevents colorectal cancer in mice. ICR mice were treated with azoxymethane and the ulcerative colitis inducer, dextran sodium sulfate, to induce colorectal tumors. Aspirin was orally administered three times per week for 12 weeks. Aspirin significantly reduced the number and size of colorectal tumors. Aspirin also significantly decreased tumor necrosis factor alpha and reactive oxygen species (ROS) levels in the plasma. Immunohistochemical analyses and western blots showed that cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), and the active form of Yes-associated protein 1 (YAP1), and cytosolic high mobility group box 1 (HMGB1) were strongly expressed at colorectal tumor sites and clearly suppressed by aspirin. An indicator of inflammation-related DNA damage, 8-nitroguanine, also accumulated in the colorectal tissues and was suppressed by aspirin. The present results suggest that the ingestion of aspirin suppressed carcinogenesis caused by inflammation through decreases in COX2 and ROS levels, resulting in reductions in DNA damage and oncogenic YAP1.
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410289920606889602","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000414221244"}],"foaf:name":[{"@language":"en","@value":"Ohnishi Shiho"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science"}]},{"@id":"https://cir.nii.ac.jp/crid/1410289920606889472","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000414221245"}],"foaf:name":[{"@language":"en","@value":"Hiramoto Keiichi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science"}]},{"@id":"https://cir.nii.ac.jp/crid/1410289920606889601","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000414221246"}],"foaf:name":[{"@language":"en","@value":"Ma Ning"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Graduate School of Health Science, Suzuka University of Medical Science"}]},{"@id":"https://cir.nii.ac.jp/crid/1410289920606889600","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000414221247"}],"foaf:name":[{"@language":"en","@value":"Kawanishi Shosuke"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"09120009"},{"@type":"EISSN","@value":"18805086"}],"prism:publicationName":[{"@language":"en","@value":"Journal of Clinical Biochemistry and Nutrition"},{"@language":"ja","@value":"Ｊｏｕｒｎａｌ ｏｆ Ｃｌｉｎｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｔｒｉｔｉｏｎ"},{"@language":"en","@value":"J. Clin. Biochem. Nutr."},{"@language":"ja","@value":"Ｊ． Ｃｌｉｎ． Ｂｉｏｃｈｅｍ． Ｎｕｔｒ．"}],"dc:publisher":[{"@language":"en","@value":"SOCIETY FOR FREE RADICAL RESEARCH JAPAN"},{"@language":"ja","@value":"一般社団法人 日本酸化ストレス学会"}],"prism:publicationDate":"2021","prism:volume":"69","prism:number":"3","prism:startingPage":"265","prism:endingPage":"271"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.jstage.jst.go.jp/article/jcbn/69/3/69_20-189/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2022251470"}],"availableAt":"2021","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=inflammation","dc:title":"inflammation"},{"@id":"https://cir.nii.ac.jp/all?q=reactive%20oxygen%20species","dc:title":"reactive oxygen species"},{"@id":"https://cir.nii.ac.jp/all?q=cyclooxygenase%202","dc:title":"cyclooxygenase 2"},{"@id":"https://cir.nii.ac.jp/all?q=yes-associated%20protein%201","dc:title":"yes-associated protein 1"},{"@id":"https://cir.nii.ac.jp/all?q=8-nitroguanine","dc:title":"8-nitroguanine"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002216818653440","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TNF-α/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619421108608","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"YAP and TAZ: a signalling hub of the tumour microenvironment"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619838344320","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302865738220672","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567185767949952","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β‐endorphin and methionine‐enkephalin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093948792704","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Complex roles of the old drug aspirin in cancer chemoprevention and therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094054950144","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094131091200","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094347939712","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094484826112","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Colorectal cancer in inflammatory bowel disease: review of the evidence"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096188551040","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hippo Coactivator YAP1 Upregulates SOX9 and Endows Esophageal Cancer Cells with Stem-like Properties"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846643598585728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"DNA Damage in Inflammation-Related Carcinogenesis and Cancer Stem Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846645608126080","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848655419846016","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Immunohistochemical Analysis of 8-Nitroguanine, A Nitrative DNA Lesion, in Relation to Inflammation-Associated Carcinogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569592786304","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Identification of Sox9-Dependent Acinar-to-Ductal Reprogramming as the Principal Mechanism for Initiation of Pancreatic Ductal Adenocarcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1361412895374348416","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chemoprevention of colorectal cancer: Past, present, and future"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519405687680","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inflammation and cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468827141504","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inducible nitric oxide synthase‐dependent DNA damage in mouse model of inflammatory bowel disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981470201861376","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"COX-2 Forms Regulatory Loop with YAP to Promote Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981470783412608","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"General Aspects of Primary Cancer Prevention"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944288765696","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Tumour YAP1 and PTEN expression correlates with tumour‐associated myeloid suppressor cell expansion and reduced survival in colorectal cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825893605232640","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Sox2 is associated with cancer stem-like properties in colorectal cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894014067200","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895442626560","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368258014080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368909361536","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"