{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:54Z","timestamp":1783660434299,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031514","name":"Health Commission of Chengdu Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Among all the most prevalent malignant gastrointestinal cancers, colorectal cancer (CRC) occurs frequently in all the populations around the world. Despite remarkable advances in related research, substantial obstacles persist in the prevention and treatment of this malignancy, including safety concerns, adverse side effects, and tumor recurrence. Natural plant-derived compounds have increasingly attracted the attention of researchers in cancer research. Among these compounds, berberine (BBR) is a natural plant substance with multiple functions, which is extracted from\n                      <jats:italic>Coptis Chinensis<\/jats:italic>\n                      that possesses strong antitumor potential. Here we aim to investigate the effects and underlying mechanisms of BBR on CRC using several organoid models developed in our laboratory.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We firstly established CRC organoid models derived from KPC transgenic mice and Caco-2 cell line. CRC organoids were treated with different doses of BBR. The morphological characteristics, proliferation, ROS, apoptosis, and cell cycle were carefully evaluated. RNA-Seq assay, epithelial permeability, and lipid probes were also used to examine the underlying molecular mechanisms of BBR on CRC organoids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BBR exhibited no harmful impact on healthy colonic tissues. However, BBR significantly inhibited the growth of both KPC organoids and Caco-2 organoids either at the early formation stage or after the maturity. BBR greatly decreased the ratio of Ki67 and EdU positive cells in CRC organoids and increased the level of ROS in organoids. RNA-Seq data implicated that BBR exerted direct cytotoxic effects on CRC organoids by inducing cell cycle arrest and breaking down the gap junctions. Immunohistochemical (IHC) staining identified the consistent changes of cell cycle arrest and dysfunction of epithelial barrier. FD4 staining showed increased epithelial permeability. Finally, LD540 probes and qPCR identified that BBR significantly blocked the lipid synthesis in CRC organoids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, our study identifies that BBR may suppress the malignant phenotype of CRC organoids via multiple mechanisms, including blocking cell cycle progression and disrupting lipid metabolism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1855151","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:45Z","timestamp":1783657545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine restrains the expansion of colorectal cancer organoids by blocking cell cycle progression and reducing lipid synthesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Hefei","family":"Tian","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Precision Radiation in Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Cancer Hospital & Institute, Sichuan Provincial Engineering Research Center for Tumor Organoids and Clinical Transformation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Precision Radiation in Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Cancer Hospital & Institute, Sichuan Provincial Engineering Research Center for Tumor Organoids and Clinical Transformation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banghui","family":"Liu","sequence":"additional","affiliation":[{"name":"Precision Radiation in Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Cancer Hospital & Institute, Sichuan Provincial Engineering Research Center for Tumor Organoids and Clinical Transformation, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, 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