Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, China.
Integr Cancer Ther. 2024 Jan-Dec;23:15347354241247061. doi: 10.1177/15347354241247061.
To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1β, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1β mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1β, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1β after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.
为了研究解毒消症饮（JXY）对结肠炎相关结肠癌（CAC）中巨噬细胞极化的影响。建立了 CAC 的原位模型，以监测小鼠病理状态的变化。记录结肠长度、结肠肿瘤数量，并计算肝、脾和胸腺指数。采用苏木精和伊红（H&E）染色观察肠黏膜损伤和肿瘤形成。免疫组织化学（IHC）染色用于研究 JXY 对 CAC 小鼠结肠黏膜中 M1 和 M2 极化巨噬细胞的影响。对于体外实验，采用逆转录定量 PCR（RT-qPCR）和流式细胞术观察 JXY 对各种 M1 相关分子（如 IL-1β、TNF-α、iNOS、CD80、CD86）及其吞噬功能的影响，以及 M2 相关分子（如 Arg-1、CD206、IL-10）。随后，用拮抗剂（TAK242、PDTC、KG501、SR11302、LY294002）拮抗 TLR4 通路后，通过 RT-qPCR 检测 IL-6、TNF-α、iNOS 和 IL-1β mRNA 的表达。体内实验结果表明，JXY 改善了小鼠的一般病理状况。与未治疗的 CAC 小鼠相比，JXY 治疗可减少结肠长度缩短和肿瘤数量。此外，JXY 治疗改善了结肠组织的病变，并诱导肠道黏膜巨噬细胞向 M1 表型极化，同时抑制向 M2 表型极化。体外实验进一步证实，JXY 治疗促进了巨噬细胞向 M1 表型的激活，导致 IL-1β、TNF-α、iNOS、CD80、CD86 的表达增加，并增强了吞噬功能。JXY 治疗同时抑制 M2 表型相关分子精氨酸酶-1（Arg-1）、CD206 和 IL-10 的表达。此外，拮抗 TLR4 通路后，JXY 抑制了 M1 相关分子如 IL-6、TNF-α、iNOS 和 IL-1β 的表达。显然，JXY 可通过 TLR4 介导的信号通路促进 M1 极化，抑制巨噬细胞 M2 极化，从而抑制 CAC 小鼠结肠肿瘤的发展。
