Antitumor properties of triptolide: phenotype regulation of macrophage differentiation
Antitumor properties of triptolide: phenotype regulation of macrophage differentiation
复制标题
雷公藤甲素的抗肿瘤特性：巨噬细胞分化的表型调节
DOI：
10.1080/15384047.2019.1679555
复制
发表时间：
2019-10-30
影响因子：
3.6
通讯作者：
Sun, Lixin
中科院分区：
文献类型：
--
作者：
Li, Han;Li, Liping;Sun, Lixin
摘要肿瘤相关巨噬细胞(TAM)在肿瘤的发生发展中起着重要作用，其表型一般为M2样细胞。雷公藤甲素具有独特的抗癌活性。本研究的目的是确定雷公藤内酯醇是否对TAMs的激活和促肿瘤介质的产生有影响。采用偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导的ICR-1小鼠结肠癌模型和BALB/c小鼠共接种4T1细胞和M2极化的RAW264.7细胞模型，观察雷公藤甲素对肿瘤生长的抑制作用是否通过靶向TAMs介导。实时定量聚合酶链式反应、Western印迹、免疫荧光染色和流式细胞仪检测细胞表面标志的表达和细胞因子的产生。结果表明，雷公藤甲素抑制巨噬细胞向M2表型分化，并抑制M2巨噬细胞介导的肿瘤进展。此外，雷公藤甲素抑制CD206、精氨酸酶1和CD204等M2标志物的表达，并抑制抗炎细胞因子的分泌。因此，我们的研究表明，雷公藤甲素选择性地抑制M2极化的巨噬细胞和TAMs的功能，这种对活力、分化和细胞因子产生的抑制作用可能是其抗肿瘤作用的主要机制。我们的发现为雷公藤甲素在癌症治疗中的潜在临床应用提供了重要的信息。
ABSTRACT 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.