THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming

作者：Zhiqin Zhu, Shi Zuo, Zhiqi Zhu, Chen Wang, Yangfeng Du, Fengsheng Chen · 发表于：International Immunopharmacology · 年份：2025 · DOI：10.1016/j.intimp.2025.114091 · 被引用次数：13 · 研究领域：Autophagy in Disease and Therapy、Epigenetics and DNA Methylation、Endoplasmic Reticulum Stress and Disease

Potential mechanisms of THSWD in treating hepatocellular carcinoma by modulating the gut microbiota, metabolic reprogramming and lysosomal autophagy signaling pathways. • THSWD effectively inhibits hepatocellular carcinoma progression by regulating intestinal flora and metabolic reprogramming. • THSWD promotes lysosomal autophagy via LTF/AMPK/mTOR/Beclin1 signalling pathway. • The anti-hepatocellular carcinoma active compounds are mainly derived from glabrol in THSWD. • THSWD mainly enriches the gut microbiota Duncaniella to remodel gut homeostasis. THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment. Metabolic analyses, transcriptomic analyses, and molecular experiments were performed to explore how THSWD modulates the gut microbiota against hepatocellular carcinoma progression. As confirmed by in vivo and in vitro assays, THSWD reduced tumour growth rate and promoted apoptosis in hepatocellular carcinoma cells in hepatocellular carcinoma model mice,...