Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling.
Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling.
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黄芪甲苷 IV 通过 AMPK 信号传导调节巨噬细胞极化来抑制肺癌进展和转移。
DOI：
10.1186/s13046-018-0878-0
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发表时间：
2018-08-29
期刊：
影响因子：
--
通讯作者：
Liu BJ
中科院分区：
文献类型：
--
作者：
Xu F;Cui WQ;Wei Y;Cui J;Qiu J;Hu LL;Gong WY;Dong JC;Liu BJ
越来越多的证据表明，M2极化的肿瘤相关巨噬细胞（tam）在癌症的进展和转移中起着重要作用，使tam的M2极化成为越来越有吸引力的治疗干预靶点。黄芪甲苷（Astragaloside IV, AS-IV）是一种从黄芪中分离出来的皂苷成分，有报道称其能抑制肺癌的侵袭和转移，但其在肺癌进展过程中对tam的影响尚未被研究。通过IL-4、IL-13和肉豆蔻酸酯phorbol acetate （PMA）诱导人THP-1单核细胞向M2巨噬细胞分化。以M2巨噬细胞（M2- cm）为培养基培养的肺癌细胞系A549和H1299为实验材料，研究AS-IV对肺癌细胞肿瘤生长、侵袭、迁移和血管生成的影响。采用流式细胞术和定量PCR分析巨噬细胞亚群分布、巨噬细胞M1和M2相关标志物及mRNA表达情况。western blotting检测介导m2 - cm促进肿瘤迁移的腺苷单磷酸活化蛋白激酶（AMPK）信号通路的激活。我们发现as - iv显著抑制IL-13和il -4诱导的巨噬细胞M2极化，表现为CD206和M2相关基因的表达降低，as - iv抑制M2- cm诱导的A549和H1299细胞的侵袭、迁移和血管生成。体内实验表明，AS-IV能显著抑制Lewis肺癌的肿瘤生长，减少肿瘤转移数。AS-IV治疗后，肿瘤组织中M2巨噬细胞百分比降低。此外，AS-IV抑制M2巨噬细胞AMPKα的活化，AMPKα的沉默部分抵消了AS-IV的抑制作用。AS-IV通过AMPK信号通路部分阻断巨噬细胞的M2极化，从而抑制肺癌的生长、侵袭、迁移和血管生成，这似乎在AS-IV抑制肺癌转移的能力中发挥了重要作用。本文的在线版本（10.1186/s13046-018-0878-0）包含补充资料，仅供授权用户使用。
Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated. Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM–promoted tumor migration was detected using western blotting. Here we found that AS-IV significantly inhibited IL-13 and IL-4–induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM–induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV. AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV’s ability to inhibit the metastasis of lung cancer. The online version of this article (10.1186/s13046-018-0878-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Qi, Weiwei;Niu, Jianying;Gu, Yong
通讯作者：
Gu, Yong
DOI：
10.1155/2013/284025
发表时间：
2013
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Tan S;Wang G;Guo Y;Gui D;Wang N
通讯作者：
Wang N
肿瘤招募的M2巨噬细胞通过M2巨噬细胞分泌的CHI3L1蛋白促进胃癌和乳腺癌转移
影响因子：
28.5
作者：
Chen Y;Zhang S;Wang Q;Zhang X
通讯作者：
Zhang X
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
黄芪甲苷 IV 对卵清蛋白诱导的慢性实验性哮喘的抑制作用。
影响因子：
2.1
作者：
Du, Qiang;Chen, Zhen;Yin, Kai-sheng
通讯作者：
Yin, Kai-sheng