Chang-wei-qing, a Chinese herbal formula, ameliorates colitis-associated tumour development via inhibiting NF-κB and STAT3 signalling pathway

Abstract

Context: Chang-wei-qing (CWQ) is a Chinese herbal recipe with clinical efficacy. However, the molecular mechanism underlying its recognized therapeutic benefits against colorectal cancer is still elusive. Objective: To investigate the potential beneficial effects of CWQ in drug-induced colitis-associated cancer (CAC) model and its mechanistic involvements in this disease. Materials and methods: Colitis-associated cancer model was induced by azoxymethane (AOM) and dextran sulphate sodium (DSS). CWQ was administrated by gavage. Colon length and tumour size were determined after resection. The colitis was systematically scored. The microbiota and population of Faecalibacterium prausnitzii (F. prausnitzii) Hauduroy & Duncan was analysed by quantitative polymerase chain reaction (PCR). β-Glucuronidase, d-lactose and endotoxin were determined with commercially available kits. Pro-inflammatory cytokines were analysed in the colon tissues. Relative protein expressions were determined by Western blotting. Results: High concentration CWQ significantly restored the colon length, decreased tumour number and size (1.7 ± 0.6 vs. 2.8 ± 0.4 mm, p < 0.01) and reduced colitis score (11.8 ± 2.1 vs. 18.2 ± 2.3, p < 0.01). CWQ also suppressed expansion of F. prausnitzii population (0.029 ± 0.015% vs. 0.052 ± 0.019%, p < 0.01). CWQ greatly inhibited the activity of β-glucuronidase and leakage of d-lactose and endotoxin. Meanwhile, the pro-inflammatory cytokines were remarkably decreased in CAC mice in response to CWQ treatment. We further demonstrated that CWQ inhibited both NF-κB and STAT3 signalling. Conclusions: We for the first time demonstrated the antitumour properties of CWQ in vivo via inhibiting NF-κB and STAT3 signalling.

Keywords

• colitis-associated cancer
• β-glucuronidase
• pro-inflammatory response