{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:40:26Z","timestamp":1764571226309,"version":"3.46.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Chemotherapy remains the mainstay treatment for gallbladder cancer; however, its therapeutic efficacy is limited by poor chemosensitivity. Therefore, identifying more effective treatment strategies is essential for improving patient prognosis. In this study, we evaluated the antitumor activity of a novel PPAR\u03b3 agonist, PG-4c, in gallbladder cancer and assessed its in vivo toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human gallbladder cancer cells were treated with PG-4c to examine its effects on the cell cycle, apoptosis, invasion, migration, and intracellular apoptotic signaling. A xenograft tumor model was used to assess the antitumor efficacy of PG-4c in vivo. Toxicity associated with PG-4c was evaluated in both mice and zebrafish.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PG-4c exhibited stronger anticancer activity than the standard chemotherapeutic agent gemcitabine. Its antitumor mechanisms involved inducing cell-cycle arrest, apoptosis, and necrosis through elevated intracellular reactive oxygen species levels and activation of cleaved caspase-3. PG-4c also impaired actin assembly, thereby inhibiting migration and invasion. In vivo, PG-4c significantly suppressed tumor growth in both zebrafish and mouse xenograft models. Notably, PG-4c demonstrated lower toxicity than the traditional PPAR\u03b3 agonist pioglitazone, as supported by animal toxicity assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings suggest that PG-4c holds strong potential as an effective chemotherapeutic candidate for gallbladder cancer. Given that PPAR\u03b3 agonists are clinically approved drugs for dyslipidemia and diabetes, this class of agents may represent a promising new therapeutic approach for gallbladder cancer management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1704994","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:26:28Z","timestamp":1764570388000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-gallbladder cancer activities and toxicity studies of glycyrrhetinic acid derivative as a novel PPAR\u03b3 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