{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:19:44Z","timestamp":1790965184760,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Science Foundation","award":["IP-2016-06-1441"],"award-info":[{"award-number":["IP-2016-06-1441"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ehrlich ascites tumor (EAT) is a rapidly growing, angiogenesis-dependent tumor characterized by high levels of vascular endothelial growth factor (VEGF). VEGF contributes to ascites formation, which supports tumor cell growth and the accumulation of tumor-associated macrophages (TAMs), primarily of the immunosuppressive M2 phenotype. M2 macrophages promote tumor progression by secreting angiogenic and immunomodulatory factors such as VEGF, matrix metalloproteinases (MMPs), and cyclooxygenase-2 (COX-2). This study investigated the effects of tannic acid (TA) on tumor growth and angiogenesis in EAT-bearing mice, focusing on TAM\u2013tumor cell interactions. We evaluated ascites volume, cell counts, macrophage activity, peritoneal angiogenesis and blood vessel density, concentrations of VEGF, COX-2, and MMP-2\/-9, blood biomarkers, and DNA damage using the comet assay. TA treatment significantly reduced tumor growth and angiogenesis by modulating TAM function. Specifically, TA inhibited VEGF, COX-2, and MMP-2\/-9 expression, decreased M2 macrophage numbers, and enhanced the antitumor immune response, as shown by increased lymphocyte activation and favorable shifts in lymphocyte-to-monocyte (LMR) and neutrophil-to-lymphocyte (NLR) ratios. Additionally, TA induced DNA fragmentation in tumor and blood cells, indicating cytotoxicity and potential induction of apoptosis. These findings suggest that TA\u2019s inhibition of TAMs may be a promising strategy for treating tumors and other angiogenesis-related conditions.<\/jats:p>","DOI":"10.3390\/ijms26189070","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:54:26Z","timestamp":1758200066000},"page":"9070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antitumor and Antiangiogenic Effect of Tannic Acid in the Advanced Stage of Ehrlich Ascites Tumor in Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-3606","authenticated-orcid":false,"given":"Nada","family":"Or\u0161oli\u0107","sequence":"first","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kun\u0161ti\u0107","sequence":"additional","affiliation":[{"name":"Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-3919","authenticated-orcid":false,"given":"Maja","family":"Jazvin\u0161\u0107ak Jembrek","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka Cesta 54, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Catholic University of Croatia, Ilica 244, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.3748\/wjg.v11.i35.5455","article-title":"Cancer-derived VEGF plays no role in malignant ascites formation in the mouse","volume":"11","author":"Guleng","year":"2005","journal-title":"World J. 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