Oleanolic acid inhibits macrophage differentiation into the M2 phenotype and glioblastoma cell proliferation by suppressing the activation of STAT3
Oleanolic acid inhibits macrophage differentiation into the M2 phenotype and glioblastoma cell proliferation by suppressing the activation of STAT3
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DOI：
10.3892/or.2011.1454
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发表时间：
2011-12-01
期刊：
影响因子：
4.2
通讯作者：
Takeya, Motohiro
中科院分区：
文献类型：
--
作者：
Fujiwara, Yukio;Komohara, Yoshihiro;Takeya, Motohiro
极化为M2表型的肿瘤相关巨噬细胞（TAM）促进肿瘤细胞增殖，并与高级别胶质瘤患者的不良预后相关。我们以前发现科罗索酸，一种三萜类化合物，抑制人单核细胞衍生的巨噬细胞（HMDM）的M2极化。在本研究中，我们研究了是否油酸（OA），一种三萜类化合物，其结构类似于科罗索酸，也表现出抑制作用的M2极化在HMDM。OA显著抑制M2巨噬细胞表型标志物之一CD 163的表达，以及抑制M2巨噬细胞优先产生的抗炎细胞因子之一IL-10的分泌，从而表明OA抑制巨噬细胞的M2极化。此外，OA抑制U373人胶质母细胞瘤细胞的增殖，以及人巨噬细胞和胶质母细胞瘤细胞中的信号转导子和转录激活子-3（STAT 3）的激活。这些结果表明，OA通过抑制STAT 3的活化来抑制巨噬细胞的M2极化和肿瘤细胞增殖。因此，OA可能是一种潜在的新药物，可用于预防和治疗各种恶性肿瘤，包括胶质瘤。
Tumor-associated macrophages (TAMs) polarized to the M2 phenotype promote tumor cell proliferation and are associated with a poor prognosis in patients with high grade glioma. We previously revealed that corosolic acid, a triterpenoid compound, inhibits the M2 polarization of human monocyte-derived macrophages (HMDM). In the present study, we examined whether oleanolic acid (OA), a triterpenoid compound whose structure is similar to corosolic acid, also shows inhibitory effects on M2 polarization in HMDM. OA significantly inhibited the expression of CD163, one of the phenotype markers of M2 macrophages, as well as suppressed the secretion of IL-10, one of the anti-inflammatory cytokines preferentially produced by M2 macrophages, thus suggesting that OA suppresses the M2 polarization of macrophages. Furthermore, OA inhibited the proliferation of U373 human glioblastoma cells, and the activation of signal transducer and activator of transcription-3 (STAT3) in both human macrophages and glioblastoma cells. These results indicate that OA suppresses the M2 polarization of macrophages and tumor cell proliferation by inhibiting STAT3 activation. Therefore, OA may be a potentially new agent that can be used for the prevention and treatment of various malignant tumors, including glioma.