Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation.

Abstract

CONTEXT\nTanshinone IIA is a natural extract derived from a Chinese medicinal herb with multiple bioactivities; however, whether and how tanshinone IIA protects against colorectal cancer (CRC) are uncertain.\n\n\nOBJECTIVE\nWe investigated the potential beneficial effects of tanshinone IIA in a colitis-associated colorectal tumorigenesis mouse model and its underlying mechanisms.\n\n\nMATERIALS AND METHODS\nMale C57BL/6 mice were treated with azoxymethane (AOM) 10\u2009mg/kg body weight and dextran sulphate sodium (2.5% DSS) to induce a colitis-associated cancer model. Tanshinone IIA (200\u2009mg/kg body weight) was given to the mice intraperitoneally. After 12\u2009weeks, all mice were sacrificed to measure tumour formation, intestinal permeability, neutrophil infiltration, and colonic inflammation. In addition, whether tanshinone IIA has inhibitory effects on neutrophil activation was determined through in\xa0vitro investigations.\n\n\nRESULTS\nWe observed that tanshinone IIA significantly decreased tumour formation in AOM/DSS-treated mice compared to AOM/DSS-treated alone mice (0.266\u2009±\u20090.057 vs. 0.78\u2009±\u20090.153, p\u2009=\u20090.013). Tanshinone IIA also decreased intestinal permeability compared to that in AOM/DSS-treated alone mice (3.12\u2009±\u20090.369 vs. 5.06\u2009±\u20090.597, p\u2009=\u20090.034) and consequently reduced neutrophil infiltration of the colonic mucosa (53.25\u2009±\u20098.85 vs. 107.6\u2009±\u200913.09, p\u2009=\u20090.014) as well as intestinal inflammation in mice. Mechanistically, tanshinone IIA downregulated the NF-κB signalling pathway in the colonic tumours of AOM/DSS-treated mice. In vitro assays further validated that tanshinone IIA suppressed LPS-induced neutrophil activation.\n\n\nCONCLUSION\nThese data suggest that tanshinone IIA alleviates colorectal tumorigenesis through inhibition of intestinal inflammation. Tanshinone IIA may have a therapeutic potential for CRC in clinical practice.