Gut microbiota derived DCA enhances FOLFOX efficacy via Ugt1a6b mediated enterohepatic circulation in colon cancer

Pharmacological Research, Journal Year: 2025, Volume and Issue: 213, P. 107636 - 107636

Published: Feb. 1, 2025

FOLFOX (5-Fluorouracil, Calcium Folinate combined with Oxaliplatin) is a preferred chemotherapy regimen for colon cancer, but its limited efficacy remains major challenge, significantly impairs patient outcomes. There an urgent need to identify strategies improve therapeutic effectiveness. Our previous studies have suggested that gut microbiota-derived bile acids may be involved in the anticancer effect of vitro, however, underlying mechanism unclear. In this study, we investigated role modulating and related mechanisms. We first demonstrated depletion (cholestyramine treatment) enhanced orthotopic cancer mouse model, suggesting play key FOLFOX's effects. Further, based on system screen 15 via MTT, colony formation flow cytometry assay, Deoxycholic Acid (DCA) Glycodeoxycholic (GDCA) were annotated as potential modulators efficacy. Among these, DCA was further validated enhance anti-colon effects vivo. Transcriptomic analysis subsequent biological experiments revealed Ugt1a6b. conclusion, our findings establish enhances potentially Ugt1a6b mediated enterohepatic circulation, providing novel insights into synergistic strategy improving treatment.

Language: Английский

Enhancing survival outcomes in unresectable hepatocellular carcinoma: a prospective cohort study on the effects of Huaier granules with targeted therapy plus immunotherapy

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Objective This study evaluated the clinical efficacy of Huaier granules combined with targeted therapy plus immunotherapy in patients unresectable hepatocellular carcinoma (HCC) who had not undergone systemic treatment. Methods Patients HCC and no prior treatments were recruited from Hospital Traditional Chinese Medicine Xinjiang First Affiliated Medical University between March 2022 July 2023. received (exposure group) or without Granules (non-exposure group). The primary endpoint was progression-free survival (PFS), secondary endpoints including 6-month PFS rate, Symptom Severity Quantitative Response, EORTC QLQ-HCC18 Score, safety. Results mPFS exposure group 8.9 months compared to 5 non-exposure (P = 0.001; HR 0.50). rates 66.7% 34.1% for groups, respectively 0.001). rate TCM symptom classification higher (87.50% vs 59.09%; P also showed improvement fatigue 0.023). Extrahepatic metastasis an independent prognostic factor (HR 1.77; 0.016), while reduced risk disease progression by 47% 0.53; 0.006). No significant differences observed adverse events. most common events hypertension, proteinuria, abnormal liver function, diarrhea. Conclusion significantly prolong improve reducing patients. Subgroup analysis more pronounced benefits vascular invasion alcohol consumption, extending beyond 1 year.

Language: Английский

Huaier inhibits the proliferation and migration of gastrointestinal stromal tumors by regulating the JAK2 / STAT3 signaling pathway

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119389 - 119389

Published: Jan. 1, 2025

Language: Английский