Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China.
Department of Anorectal, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China.
J Ethnopharmacol. 2024 Nov 15;334:118541. doi: 10.1016/j.jep.2024.118541. Epub 2024 Jul 9.
Based on the core pathogenesis of hepatosplenic disorder and qi transformation disorder in ulcerative colitis, Tong-Xie-Yao-Fang (TXYF) is a classical traditional Chinese medicine commonly used to treat ulcerative colitis. Our study revealed that it has the potential to prevent colitis-associated colorectal cancer, which embodies the academic concept in traditional Chinese medicine of treating the disease before it develops.
This study was aimed at evaluating the therapeutic role of TXYF in treating colitis-associated colorectal cancer and exploring its possible underlying mechanisms.
A colitis-associated colorectal cancer model was established in mice using azoxymethane and dextran sulfate sodium salt to examine the therapeutic effect of TXYF. The mouse body weights were observed. Hematoxylin-eosin staining was used to evaluate mouse colon histopathology. Colon cancer cells and colon epithelial cells were used to explore the potential molecular mechanisms. The proliferation and apoptosis of cells were detected by CCK8 and cell colony assays, flow cytometry and western blotting. The epithelial-mesenchymal transition (EMT) and mitophagy markers were examined by immunohistochemistry, western blotting, quantitative real-time PCR and immunofluorescence staining.
TXYF inhibited the tumorigenesis of mice with colitis-associated colorectal cancer and the growth of inflammatory colon cells. TXYF induced mitophagy in colon cancer cells through the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway to reverse EMT, which was consistent with the results in mice with colitis-associated colorectal cancer.
The results of the present study demonstrated that TXYF effectively inhibited the progression of colitis-associated colorectal cancer through the PINK1/Parkin pathway, which provides new evidence for prevention strategies for this disease.
基于溃疡性结肠炎的肝脾失调和气机失调的核心发病机制，痛泻要方（TXYF）是一种常用于治疗溃疡性结肠炎的经典中药。我们的研究表明，它具有预防结肠炎相关结直肠癌的潜力，这体现了中医“治未病”的学术理念。
本研究旨在评估痛泻要方治疗结肠炎相关结直肠癌的作用，并探讨其可能的潜在机制。
采用氧化偶氮甲烷和葡聚糖硫酸钠盐建立结肠炎相关结直肠癌小鼠模型，以考察痛泻要方的治疗作用。观察小鼠体重，苏木精-伊红染色评估小鼠结肠组织病理学变化。使用结肠癌细胞和结肠上皮细胞探讨潜在的分子机制。通过 CCK8 和细胞集落实验、流式细胞术和 Western blot 检测细胞增殖和凋亡。通过免疫组化、Western blot、实时定量 PCR 和免疫荧光染色检测上皮-间充质转化（EMT）和噬线粒体的标记物。
痛泻要方抑制了结肠炎相关结直肠癌小鼠的肿瘤发生和炎症性结肠细胞的生长。痛泻要方通过 PTEN 诱导的假定激酶 1（PINK1）/Parkin 通路诱导结肠癌细胞发生噬线粒体作用，从而逆转 EMT，这与结肠炎相关结直肠癌小鼠的结果一致。
本研究结果表明，痛泻要方通过 PINK1/Parkin 通路有效抑制了结肠炎相关结直肠癌的进展，为该疾病的预防策略提供了新的证据。
