Astragalus Polysaccharide (PG2) Suppresses Macrophage Migration Inhibitory Factor and Aggressiveness of Lung Adenocarcinoma Cells
Astragalus Polysaccharide (PG2) Suppresses Macrophage Migration Inhibitory Factor and Aggressiveness of Lung Adenocarcinoma Cells
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DOI：
10.1142/s0192415x20500731
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发表时间：
2020-01-01
影响因子：
5.7
通讯作者：
Yao, Chih-Jung
中科院分区：
文献类型：
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作者：
Liao, Chien-Huang;Yong, Chen-Yin;Yao, Chih-Jung
黄芪是最受欢迎的传统中药用于管理气虚。其可注射多糖PG 2已被用于缓解癌症相关的疲劳，PG 2具有免疫调节和抗炎作用。本研究探讨了PG 2对肺腺癌A549和CL 1 -2细胞的作用及其抗肿瘤活性，并在重症联合免疫缺陷（SCID）小鼠中进行了验证。虽然PG 2没有抑制这些细胞的生长，但它剂量依赖性地抑制它们的迁移和侵袭，伴随着减少波形蛋白和AXL和诱导上皮钙粘蛋白（E-cadherin）的表达。关于潜在的分子机制，PG 2治疗减少了巨噬细胞迁移抑制因子（MIF），这是一种促进上皮-间充质转化和癌细胞侵袭性的炎性细胞因子。与先前发现的MIF调节基质金属蛋白酶-13（MMP-13）和AMP活化蛋白激酶（AMPK）一致，在本研究中，用PG 2处理降低了A549和CL 1 -2细胞中的MMP-13并活化了AMPK。在通过尾静脉注射A549细胞的SCID小鼠中，腹膜内注射PG 2减少了肺和腹部转移，同时减少了肿瘤中AXL、波形蛋白、MMP-13和MIF的免疫组织化学染色。总的来说，数据揭示了PG 2通过抑制癌细胞中的MIF及其侵袭性在综合癌症治疗中的潜在应用。
Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.