Jiedu Xiaozheng Yin Inhibits the Progression of Colitis Associated Colorectal Cancer by Stimulating Macrophage Polarization Towards an M1 Phenotype via the TLR4 Pathway

IF 2.9 3区医学 Q2 INTEGRATIVE & COMPLEMENTARY MEDICINE

Integrative Cancer Therapies Pub Date : 2024-04-20 DOI:10.1177/15347354241247061

Haiqin Liu, Shuo Yan, Ruiming Yang, Caidi Huang, Kangyue Guo, Shi Wang, Yunmei Huang, Dongyi Shen, Ying Lin, Zhiyun Cao, Hangyan Zhong, Jiumao Lin, Xuzheng Chen

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引用次数: 0

Abstract

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.

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解毒小柴胡汤通过TLR4途径刺激巨噬细胞向M1表型极化，从而抑制结肠炎相关性结直肠癌的进展

研究解郁安神汤（JXY）对结肠炎相关性结肠癌（CAC）巨噬细胞极化的影响。建立 CAC 正位模型，监测小鼠病理状态的变化。记录结肠长度、结肠肿瘤数量，并计算肝脏、脾脏和胸腺指数。采用苏木精和伊红（H&E）染色观察肠粘膜损伤和肿瘤形成。免疫组化（IHC）染色用于研究 JXY 对 CAC 小鼠结肠粘膜巨噬细胞 M1 和 M2 极化的影响。在体外实验中，使用 RT-qPCR（逆转录-定量 PCR）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）以及 M2 相关分子（包括 Arg-1、CD206 和 IL-10）的影响。随后，用拮抗剂（TAK242、PDTC、KG501、SR11302、LY294002）拮抗 TLR4 通路后，用 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 可改善小鼠的总体病理状况。与未接受 JXY 治疗的 CAC 小鼠相比，接受 JXY 治疗的小鼠结肠长度缩短，肿瘤数量减少。此外，JXY 还能改善结肠组织的病变，诱导肠粘膜巨噬细胞向 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 处理可促进巨噬细胞向 M1 表型活化，导致 IL-1β、TNF-α、iNOS、CD80、CD86 的表达增加，并增强吞噬功能。JXY 处理可同时抑制 M2 型相关分子精氨酸酶-1（Arg-1）、CD206 和 IL-10 的表达。此外，在拮抗 TLR4 通路后，JXY 还能抑制 IL-6、TNF-α、iNOS 和 IL-1β 等 M1 型相关分子的表达。显然，JXY通过TLR4介导的信号传导促进巨噬细胞的M1极化，阻碍巨噬细胞的M2极化，从而对CAC小鼠结肠肿瘤的发展起到抑制作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Integrative Cancer Therapies 医学-全科医学与补充医学

CiteScore

4.80

自引率

3.40%

发文量

审稿时长

>12 weeks

期刊介绍： ICT is the first journal to spearhead and focus on a new and growing movement in cancer treatment. The journal emphasizes scientific understanding of alternative medicine and traditional medicine therapies, and their responsible integration with conventional health care. Integrative care includes therapeutic interventions in diet, lifestyle, exercise, stress care, and nutritional supplements, as well as experimental vaccines, chrono-chemotherapy, and other advanced treatments. Contributors are leading oncologists, researchers, nurses, and health-care professionals.