Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier

作者：Ruolei Wang, Fengjing Jia, Zhenguo Zhao, Liqing Du, Lianheng Lu, Dongkui Xu, Feng He · 发表于：Cancer Pathogenesis and Therapy · 年份：2023 · DOI：10.1016/j.cpt.2023.02.003 · 被引用次数：9 · 研究领域：Biochemical Acid Research Studies、Metabolomics and Mass Spectrometry Studies、Lipid metabolism and disorders

Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vas...