Zhang Yunsha, Pu Weiling, Bousquenaud Mélanie, Cattin Sarah, Zaric Jelena, Sun Li-Kang, Rüegg Curzio
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Pathology Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Front Oncol. 2021 Jan 8;10:564674. doi: 10.3389/fonc.2020.564674. eCollection 2020.
Colorectal cancer (CRC) is one of the most common cancer worldwide. Chronic inflammation contributes to CRC development and progression. Emodin, is a natural anthraquinone derivative with anti-oxidant, anti-inflammatory, and anti-tumor activities. We used the AOM/DSS model of colitis-associated intestinal tumorigenesis to characterize the effect of Emodin on inflammation and tumorigenesis at weeks 3, 5, and 14 after initiation with AOM. At all three time points, Emodin (50 mg/kg) reduced inflammatory cell (i.e. CD11b and F4/80) recruitment, cytokine (i.e. TNFα, IL1α/β, IL6, CCL2, CXCL5) and pro-inflammatory enzymes (i.e. COX-2, NOS2) expression in the tumor microenvironment, while promoting recruitment of CD3 T lymphocytes at 14 weeks. Emodin decreased the incidence of premalignant lesions (adenoma) at week 3, the incidence of dysplastic lesions and carcinomas at week 5, and the incidence, size and the invasiveness of carcinomas at week 14. Emodin also reduced the acute clinical intestinal symptoms (i.e. bleeding and diarrhea) during DSS treatment. , Emodin inhibited the expression of pro-inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, and reduced viability, adhesion, migration, and fibroblasts-induced invasion of SW620 and HCT116 colon cancer cells. In conclusion, this work demonstrates that Emodin suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression. These results instigate further studies on Emodin as a natural agent for the prevention or treatment of colorectal cancer.
结直肠癌（CRC）是全球最常见的癌症之一。慢性炎症促进结直肠癌的发生和发展。大黄素是一种天然蒽醌衍生物，具有抗氧化、抗炎和抗肿瘤活性。我们使用结肠炎相关肠道肿瘤发生的AOM/DSS模型，来表征大黄素在AOM启动后第3、5和14周对炎症和肿瘤发生的影响。在所有三个时间点，大黄素（50mg/kg）减少了肿瘤微环境中炎性细胞（即CD11b和F4/80）的募集、细胞因子（即TNFα、IL1α/β、IL6、CCL2、CXCL5）和促炎酶（即COX-2、NOS2）的表达，同时在第14周促进CD3 T淋巴细胞的募集。大黄素在第3周降低了癌前病变（腺瘤）的发生率，在第5周降低了发育异常病变和癌的发生率，在第14周降低了癌的发生率、大小和侵袭性。大黄素还减轻了DSS治疗期间的急性临床肠道症状（即出血和腹泻）。大黄素抑制LPS刺激的RAW 264.7巨噬细胞中促炎介质的表达，并降低SW620和HCT116结肠癌细胞的活力、粘附、迁移和成纤维细胞诱导的侵袭。总之，这项工作表明大黄素抑制致癌相关的肠道炎症，并预防AOM/DSS诱导的肠道肿瘤发生和进展。这些结果促使对大黄素作为预防或治疗结直肠癌的天然药物进行进一步研究。
