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用大孔树脂从淫羊藿中纯化淫羊藿苷的工艺优化及淫羊藿苷对肿瘤免疫微环境的调控作用。

Optimization of the process for purifying icariin from Herba Epimedii by macroporous resin and the regulatory role of icariin in the tumor immune microenvironment.

机构信息

Tianjin Key Laboratory of Acute Abdominal Disease-Associated Organ Injury and ITCWM Repair, Institute ofAcute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, 300100, China; Department of General Surgery, The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China.

Tianjin Key Laboratory of Acute Abdominal Disease-Associated Organ Injury and ITCWM Repair, Institute ofAcute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, 300100, China.

出版信息

Biomed Pharmacother. 2019 Oct;118:109275. doi: 10.1016/j.biopha.2019.109275. Epub 2019 Aug 2.

Abstract

Pancreatic cancer is a digestive tract malignancy that poses a serious threat to human health. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to regulate the tumor immune microenvironment in patients with pancreatic cancer. In this study, icariin was purified from Herba Epimedii using macropores, and its bioactivity against pancreatic cancer was also investigated. We found that icariin has direct inhibitory and immunomodulatory effects on tumor cells. In vitro experiments showed that icariin can inhibit the migration and proliferation of Panc02 pancreatic cancer cells and induce apoptosis. Our in vivo experiments show that icariin inhibits the development of mouse pancreatic cancer by inhibiting tumor-infiltrating M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (MDSCs) (PMN-MDSCs). In addition, icariin inhibits the polarization of RAW 264.7 cells into M2 macrophages by inhibiting the expression of ARG1 and MRC1 and downregulating the IL4-STAT6 signaling pathway. In conclusion, the inhibitory effect of icariin on pancreatic cancer can not only directly affect tumor cells but also inhibit tumor development by regulating the tumor immune microenvironment.

摘要

胰腺癌是一种消化道恶性肿瘤,严重威胁人类健康。从中药中提取的化合物一直是抗癌药物和调节肿瘤免疫微环境的辅助药物的重要来源,用于治疗胰腺癌患者。在这项研究中,淫羊藿苷通过大孔树脂从淫羊藿中被分离出来,同时也研究了其对胰腺癌的生物活性。我们发现淫羊藿苷对肿瘤细胞具有直接的抑制和免疫调节作用。体外实验表明,淫羊藿苷可抑制 Panc02 胰腺癌细胞的迁移和增殖,并诱导其凋亡。我们的体内实验表明,淫羊藿苷通过抑制肿瘤浸润的 M2 巨噬细胞和多形核髓系来源的抑制性细胞(PMN-MDSCs)抑制小鼠胰腺癌的发展。此外,淫羊藿苷通过抑制 ARG1 和 MRC1 的表达和下调 IL4-STAT6 信号通路,抑制 RAW 264.7 细胞向 M2 巨噬细胞的极化。总之,淫羊藿苷对胰腺癌的抑制作用不仅可以直接影响肿瘤细胞,还可以通过调节肿瘤免疫微环境抑制肿瘤的发展。

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