Department of Oncology, Shanghai Dermatology Hospital, Tongji University, Shanghai 200443, China; Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, PR China; Tongji University Cancer Center, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Department of Oncology, Shanghai Dermatology Hospital, Tongji University, Shanghai 200443, China; Tongji University Cancer Center, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
J Nutr Biochem. 2018 Jul;57:103-109. doi: 10.1016/j.jnutbio.2018.03.007. Epub 2018 Mar 17.
Reduced short-chain fatty acids (SCFAs) have been reported in patients with ulcerative colitis, and increased intake of dietary fiber has shown to be clinically beneficial for colitis. Whether SCFAs suppress tumorigenesis in colitis-associated colorectal cancer remains unknown. The chemopreventive effect of SCFAs in colitis-associated colorectal cancer was evaluated in this study. Model of colitis-associated colorectal cancer in male BALB/c mice was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). SCFAs mix (67.5 mM acetate, 40 mM butyrate, 25.9 mM propionate) was administered in drink water during the study period. Macroscopic and histological studies were performed to examine the colorectal inflammation and tumorigenesis in AOM/DSS-induced mice treated with or without SCFA mix. The effects of SCFAs mix on colonic epithelial cellular proliferation were also assessed using Ki67 immunohistochemistry and TUNEL staining. The administration of SCFAs mix significantly reduced the tumor incidence and size in mice with AOM/DSS-induced colitis associated colorectal cancer. SCFAs mix protected from AOM/DSS-induced colorectal cancer by improving colon inflammation and disease activity index score as well as suppressing the expression of proinflammatory cytokines including IL-6, TNF-α and IL-17. A decrease in cell proliferation markers and an increase in TUNEL-positive tumor epithelial cells were also demonstrated in AOM/DSS mice treated with SCFAs mix. SCFAs mix administration prevented development of tumor and attenuated the colonic inflammation in a mouse model of colitis-associated colorectal cancer. SCFAs mix may be a potential agent in the prevention and treatment of colitis-associated colorectal cancer.
溃疡性结肠炎患者的短链脂肪酸（SCFAs）水平降低，增加膳食纤维的摄入对结肠炎具有临床益处。SCFAs 是否能抑制结肠炎相关结直肠癌的发生尚不清楚。本研究评估了 SCFAs 对结肠炎相关结直肠癌的化学预防作用。雄性 BALB/c 小鼠通过氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导结肠炎相关结直肠癌模型。在研究期间，将 SCFAs 混合物（67.5mM 乙酸盐、40mM 丁酸盐、25.9mM 丙酸盐）加入饮用水中。通过宏观和组织学研究检查 AOM/DSS 诱导的小鼠的结直肠炎症和肿瘤发生情况，这些小鼠接受或未接受 SCFA 混合物治疗。还通过 Ki67 免疫组化和 TUNEL 染色评估 SCFAs 混合物对结肠上皮细胞增殖的影响。SCFAs 混合物的给药显著降低了 AOM/DSS 诱导的结肠炎相关结直肠癌小鼠的肿瘤发生率和肿瘤大小。SCFAs 混合物通过改善结肠炎症和疾病活动指数评分以及抑制包括 IL-6、TNF-α 和 IL-17 在内的促炎细胞因子的表达，从而预防 AOM/DSS 诱导的结直肠癌。还在接受 SCFAs 混合物治疗的 AOM/DSS 小鼠中观察到细胞增殖标志物减少和 TUNEL 阳性肿瘤上皮细胞增加。SCFAs 混合物给药可预防肿瘤的发生并减轻结肠炎相关结直肠癌小鼠的结肠炎症。SCFAs 混合物可能是预防和治疗结肠炎相关结直肠癌的潜在药物。
