Sanwu Baisan decoction inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis.

Abstract

Objective: To uncover the anti-tumor effects and potential mechanism of Sanwu Baisan Decoction (, SWB) in treatment of colorectal cancer (CRC) in mice.

Methods: Therapeutic effect was evaluated based on body weight gain, tumor volume, tumor growth inhibition rate, and histological changes and apoptosis in the tumor tissues. Anti-tumor immunity was studied by measuring plasma levels of anti-tumor cytokines, interleukin 6 (IL-6), interleukin 17 (IL-17), and interferon γ (IFN-γ). Gut morphological changes were evaluated by histological staining and tight junction proteins expressions. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Classical toll-like receptor 4 (TLR-4)/ cyclooxygenase 2 (COX-2)/ prostaglandin E2 (PGE-2) pathway was examined in colon tissue and tumor samples.

Results: SWB presented high anti-tumor efficacy of CRC in mice, which manifested as decreased tumor volume and increased tumor growth inhibition rate. This anti-tumor effect of SWB was associated with elevated plasma levels of anti-tumor immune cytokines (IL-6, IL-17, and IFN-γ). Further studies showed that SWB also increases the expression of occluding and promotes the abundance of gut probiotics, , , and . Moreover, results suggested that the anti-tumor effects of SWB might associate with inducing cancer cell apoptosis and inhibiting the TLR-4/COX-2/PGE-2 pathway in both colon tissue and tumor samples.

Conclusion: SWB shows strong anti-tumor efficiency in mice with colorectal carcinoma, possibly through promoting the secretion of anti-tumor immune cytokines, inducing cancer apoptosis, maintaining the gut microbiota, and inhibiting tumorigenesis by inhibiting the TLR-4/COX-2/PGE-2 pathway.