Institute of Regenerative Medicine, Yanbian University College of Medicine, Yanji, China.
Institute of Regenerative Medicine, Yanbian University College of Medicine, Yanji, China; Department of Pathology, Yanbian University College of Medicine, Yanji, China.
Biochem Pharmacol. 2023 Nov;217:115838. doi: 10.1016/j.bcp.2023.115838. Epub 2023 Sep 29.
M2 type tumor-associated macrophages, an essential component of the tumor microenvironment (TME), have been proved to contribute to tumor metastasis. Dauricine (Dau) has recently received widespread attention due to its multiple targets and low price. However, the effect of Dau on macrophage polarization of TME remains unclear. In this study, we investigated the effect of Dau on prostate cancer (PCa) metastasis and specifically its correlation to macrophage polarization. Our results showed that Dau efficiently suppressed M2 polarization of macrophages induced by interleukin (IL) -4 and IL-13. Mechanistically, Dau inhibited the activity of PI3K/AKT signaling pathway, which subsequently suppressed macrophage differentiation to M2 type. Importantly, our study indicated that Dau decreased the release of chitinase 3-like protein 1 (CHI3L1) from M2 macrophages, which ultimately inhibited the M2 macrophage-mediated progression of PCa cells in vitro and in vivo. Taken together, our data demonstrated that Dau suppressed M2 polarization of macrophages via downregulation of the PI3K/AKT signaling pathway, in turn, preventing proliferation, epithelial-mesenchymal transition, migration, and invasion of PCa cells. Thus, this study reveals a previously unrecognized function of Dau in inhibition of PCa progression via intervention in M2 polarization of macrophages.
M2 型肿瘤相关巨噬细胞是肿瘤微环境（TME）的重要组成部分，已被证明有助于肿瘤转移。由于达乌里菌素（Dau）具有多个靶点和低廉的价格，最近受到了广泛关注。然而，Dau 对 TME 中巨噬细胞极化的影响尚不清楚。在本研究中，我们研究了 Dau 对前列腺癌（PCa）转移的影响，特别是其与巨噬细胞极化的相关性。我们的结果表明，Dau 能有效抑制白细胞介素（IL）-4 和 IL-13 诱导的巨噬细胞 M2 极化。在机制上，Dau 抑制了 PI3K/AKT 信号通路的活性，从而抑制了巨噬细胞向 M2 型分化。重要的是，我们的研究表明，Dau 降低了 M2 巨噬细胞释放的几丁质酶 3 样蛋白 1（CHI3L1），从而最终抑制了 PCa 细胞在体外和体内的 M2 巨噬细胞介导的进展。综上所述，我们的数据表明，Dau 通过下调 PI3K/AKT 信号通路抑制巨噬细胞 M2 极化，从而阻止 PCa 细胞的增殖、上皮-间充质转化、迁移和侵袭。因此，这项研究揭示了 Dau 通过干预 M2 极化抑制 PCa 进展的一个以前未被认识的功能。
