Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an, China.
Cancer Biol Ther. 2020;21(2):178-188. doi: 10.1080/15384047.2019.1679555. Epub 2019 Oct 30.
Tumor-associated macrophages (TAMs), which generally exhibit an M2-like phenotype, play a critical role in tumor development. Triptolide exerts a unique bioactive spectrum of anticancer activities. The aim of this study was to determine whether triptolide has any effect on the activation of TAMs and the production of tumor-promoting mediators. ICR-1 mice with azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors and BALB/c mice co-inoculated with 4T1 cells and M2-polarized RAW264.7 cells were used to examine whether the inhibitory effect of triptolide on tumor progression was mediated by the targeting of TAMs. Real-time PCR, Western blot, immunofluorescence staining, and flow cytometry assays were performed to determine the expression of cell surface markers and cytokine production. The results showed that triptolide inhibited macrophage differentiation toward the M2 phenotype and abolished M2 macrophage-mediated tumor progression. Furthermore, triptolide inhibited the expression of M2 markers, such as CD206, Arginase 1, and CD204, and inhibited the secretion of anti-inflammatory cytokines. Thus our study indicated that triptolide selectively inhibited the functions of M2-polarized macrophages and TAMs, and this inhibitory effect of triptolide on TAM viability, differentiation, and cytokine production might elucidate the major mechanisms underlying its antitumor activity. Our findings provide important information for the potential clinical application of triptolide in cancer therapy.
肿瘤相关巨噬细胞（TAMs）通常表现出 M2 样表型，在肿瘤发展中发挥关键作用。雷公藤红素具有独特的抗癌生物活性谱。本研究旨在确定雷公藤红素是否对 TAMs 的激活和肿瘤促进介质的产生有任何影响。我们使用 AOM/DSS 诱导的 ICR-1 小鼠结肠癌模型和共接种 4T1 细胞和 M2 极化 RAW264.7 细胞的 BALB/c 小鼠来检验雷公藤红素对肿瘤进展的抑制作用是否通过靶向 TAMs 来介导。我们通过实时 PCR、Western blot、免疫荧光染色和流式细胞术检测来确定细胞表面标志物的表达和细胞因子的产生。结果表明，雷公藤红素抑制巨噬细胞向 M2 表型分化，并消除了 M2 巨噬细胞介导的肿瘤进展。此外，雷公藤红素抑制了 M2 标志物的表达，如 CD206、精氨酸酶 1 和 CD204，并抑制了抗炎细胞因子的分泌。因此，我们的研究表明，雷公藤红素选择性地抑制了 M2 极化巨噬细胞和 TAMs 的功能，雷公藤红素对 TAM 活力、分化和细胞因子产生的抑制作用可能阐明了其抗肿瘤活性的主要机制。我们的发现为雷公藤红素在癌症治疗中的潜在临床应用提供了重要信息。
