Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, PR China.
Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223002, Jiangsu, PR China.
Pharmacol Res. 2019 Oct;148:104417. doi: 10.1016/j.phrs.2019.104417. Epub 2019 Aug 29.
Intact epithelial barrier and mucosal immune system are crucial for maintaining intestinal homeostasis. Previous study indicated that Dendrobium officinale polysaccharides (DOPS) can regulate immune responses and inflammation to alleviate experimental colitis. However, it remains largely unknown whether DOPS can suppress AOM/DSS-induced colorectal cancer (CRC) model through its direct impact on intestinal barrier function and intestinal mucosal immunity. Here, we demonstrated the therapeutic action of DOPS for CRC model and further illustrated its underlying mechanisms. Treatment with 5-aminosalicylic acid (5-ASA) and DOPS significantly improved the clinical signs and symptoms of chronic colitis, relieve colon damage, suppress the formation and growth of colon tumor in CRC mice. Moreover, administration of DOPS effectively preserved the intestinal barrier function via reducing the loss of zonula occludens-1 (ZO-1) and occludin in adjacent tissues and carcinomatous tissues. Further studies demonstrated that DOPS improved the metabolic ability of tumor infiltrated CD8 cytotoxic T lymphocytes (CTLs) and reduced the expression of PD-1 on CTLs to enhance the anti-tumor immune response in the tumor microenvironments (TME). Together, the conclusions indicated that DOPS restore intestinal barrier function and enhance intestinal anti-tumor immune response to suppress CRC, which may be a novel strategy for the prevention and treatment of CRC.
完整的上皮屏障和黏膜免疫系统对于维持肠道内环境稳态至关重要。先前的研究表明，铁皮石斛多糖（Dendrobium officinale polysaccharides，DOPS）可以调节免疫反应和炎症，从而缓解实验性结肠炎。然而，DOPS 是否可以通过直接影响肠道屏障功能和肠道黏膜免疫来抑制 AOM/DSS 诱导的结直肠癌（colorectal cancer，CRC）模型，目前在很大程度上仍不清楚。在这里，我们证明了 DOPS 对 CRC 模型的治疗作用，并进一步阐明了其潜在机制。5-氨基水杨酸（5-aminosalicylic acid，5-ASA）和 DOPS 的治疗显著改善了慢性结肠炎的临床症状和体征，缓解了结肠损伤，抑制了 CRC 小鼠结肠肿瘤的形成和生长。此外，DOPS 的给药有效地通过减少相邻组织和癌组织中闭锁蛋白-1（zonula occludens-1，ZO-1）和闭锁蛋白的丢失来维持肠道屏障功能。进一步的研究表明，DOPS 改善了肿瘤浸润 CD8 细胞毒性 T 淋巴细胞（cytotoxic T lymphocytes，CTLs）的代谢能力，并降低了 CTLs 上 PD-1 的表达，从而增强了肿瘤微环境（tumor microenvironments，TME）中的抗肿瘤免疫反应。综上所述，这些结论表明 DOPS 恢复了肠道屏障功能，并增强了肠道抗肿瘤免疫反应，从而抑制了 CRC，这可能是预防和治疗 CRC 的一种新策略。
