The combination of Brassica rapa L. polysaccharides and cisplatin enhances the anti liver cancer effect and improves intestinal microbiota and metabolic disorders

Abstract

Polysaccharides are commonly used as low-toxicity anticancer active substances to enhance the chemotherapeutic effect of cisplatin and reduce toxicity. Brassica rapa L. polysaccharides have been shown to have hepatoprotective effects; however, their anticancer effects in combination with cisplatin and their mechanisms have not been reported. An acidic polysaccharide from Brassica rapa L. (BRCPe) using hydroalcohol precipitation-assisted sonication was Characterized. The effects of BRCPe combined with cisplatin treatment on tumor growth in hepatocellular carcinoma mouse model were investigated. The impact of the combined treatment on the composition of intestinal flora, levels of short-chain fatty acids and endogenous metabolites in tumor mice were analyzed based on macrogenomic and metabolomic data Our results showed that the BRCPe combined with low-dose Cisplatin group showed better inhibitory activity against hepatocellular carcinoma cell growth in terms of tumor volume, tumor weight, and tumor suppression rate compared with the BRCPe and Cisplation alone group, and reduced the side effects of cisplatin-induced body weight loss, immune deficiency, and liver injury. Furthermore, BRCPe combined with cisplatin was found to induce apoptosis in hepatocellular carcinoma cell through the activation of the caspase cascade reaction. In addition, the intervention of BRCPe were observed to modulate the composition, structure and functional structure of intestinal flora affected by cisplatin. Notably, Lachnospiraceae bacteria, Lactobacillus murinus, Muribaculaceae, and Clostridiales bacteria were identified as significant contributors to microbial species involved in metabolic pathways. Moreover, BRCPe effectively regulate the metabolic disorders in cisplatin-induced hepatocellular carcinoma mice. In conclusion, BRCPe could potentially function as an adjuvant or dietary supplement to augment the effectiveness of cisplatin chemotherapy through the preservation of a more efficient intestinal microenvironmental homeostasis.