研究动态
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痛泻药方诱导结肠上皮细胞线粒体自噬,抑制结肠炎相关结直肠癌。

Tong-Xie-Yao-Fang Induces Mitophagy in Colonic Epithelial Cells to Inhibit Colitis-associated Colorectal Cancer.

发表日期:2024 Jul 09
作者: Zitong Xu, Gang Zhao, Lize Zhang, Cuixia Qiao, Hao Wang, Hongyun Wei, Ruiqing Liu, Penglin Liu, Yuejuan Zhang, Wei Zhu, Wenli You
来源: JOURNAL OF ETHNOPHARMACOLOGY

摘要:

痛泻要方(TXYF)以溃疡性结肠炎肝脾失常、气化失常为核心病机,是治疗溃疡性结肠炎常用的经典中药。我们的研究发现其具有预防结肠炎相关结直肠癌的潜力,体现了中医治未病的学术理念。本研究旨在评价TXYF在治疗结肠炎相关结直肠癌中的治疗作用。利用氧化偶氮甲烷和硫酸葡聚糖钠盐在小鼠中建立结肠炎相关结直肠癌模型,以检验 TXYF 的治疗效果。观察小鼠体重。苏木精-伊红染色用于评估小鼠结肠组织病理学。使用结肠癌细胞和结肠上皮细胞来探索潜在的分子机制。通过CCK-8和细胞集落实验、流式细胞仪和蛋白质印迹法检测细胞的增殖和凋亡。通过免疫组织化学、蛋白质印迹、实时定量PCR和免疫荧光染色检测上皮间质转化(EMT)和线粒体自噬标志物。TXYF抑制结肠炎相关结直肠癌小鼠的肿瘤发生和炎性结肠细胞的生长。 TXYF 通过 PTEN 诱导的推定激酶 1 (PINK1)/Parkin 通路诱导结肠癌细胞线粒体自噬,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,TXYF 有效通过 PINK1/Parkin 通路抑制结肠炎相关结直肠癌的进展,这为该疾病的预防策略提供了新的证据。版权所有 © 2024。由 Elsevier B.V. 出版。
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 CCK-8 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.Copyright © 2024. Published by Elsevier B.V.