Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling.
Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling.
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青蒿素及其衍生物通过Wnt/β-catenin信号通路显着抑制肺部肿瘤发生和肿瘤转移
DOI：
10.18632/oncotarget.8920
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Tong Y;Liu Y;Zheng H;Zheng L;Liu W;Wu J;Ou R;Zhang G;Li F;Hu M;Liu Z;Lu L
非小细胞肺癌（NSCLC）是世界范围内最常见的恶性肿瘤，其发病率高，死亡率高，预后差。据报道，抗疟疾化合物青蒿素（ART）、双氢青蒿素（DHA）和青蒿琥酯（ARTS）具有抗癌潜力，但其潜在机制尚不清楚。本研究采用流式细胞仪检测ART、DHA和ARTS对A549和H1299细胞的增殖抑制作用，结果显示ART、DHA和ARTS均能使细胞周期阻滞于G1期。同时，这些化合物还显着抑制肿瘤恶性程度，包括迁移、侵袭、癌症干细胞和上皮-间质转化。此外，ART，DHA和ARTS显着降低体内肿瘤生长。通过使用Wnt/β-catenin通路抑制剂IWP-2和Wnt 5a siRNA，我们发现ART、DHA和ARTS可以使肿瘤抑制部分依赖于Wnt/β-catenin失活。这些化合物可以显著降低Wnt 5-a/B的蛋白水平，同时增加NKD 2和Axin 2的蛋白水平，最终导致β-catenin下调。总之，我们的研究结果表明，ART，DHA和ARTS可以通过抑制Wnt/β-catenin途径抑制肺肿瘤进展，从而表明ART，DHA和ARTS在癌症治疗中的新靶点。
Non-small-cell lung cancer (NSCLC) is the most prevalent malignancy worldwide given its high incidence, considerable mortality, and poor prognosis. The anti-malaria compounds artemisinin (ART), dihydroartemisinin (DHA), and artesunate (ARTS) reportedly have anti-cancer potential, although the underlying mechanisms remain unclear. In this work, we used flow cytometry to show that ART, DHA, and ARTS could inhibit the proliferation of A549 and H1299 cells by arresting cell cycle in G1 phase. Meanwhile, tumor malignancy including migration, invasion, cancer stem cells, and epithelial–mesenchymal transition were also significantly suppressed by these compounds. Furthermore, ART, DHA, and ARTS remarkably decreased tumor growth in vivo. By using IWP-2, the inhibitor of Wnt/β-catenin pathway, and Wnt5a siRNA, we found that ART, DHA, and ARTS could render tumor inhibition partially dependent on Wnt/β-catenin inactivation. These compounds could strikingly decrease the protein level of Wnt5-a/b and simultaneously increase those of NKD2 and Axin2, ultimately resulting in β-catenin downregulation. In summary, our findings revealed that ART, DHA, and ARTS could suppress lung-tumor progression by inhibiting Wnt/β-catenin pathway, thereby suggesting a novel target for ART, DHA, and ARTS in cancer treatment.
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影响因子：
3.7
作者：
Bartis D;Csongei V;Weich A;Kiss E;Barko S;Kovacs T;Avdicevic M;D'Souza VK;Rapp J;Kvell K;Jakab L;Nyitrai M;Molnar TF;Thickett DR;Laszlo T;Pongracz JE
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Pongracz JE
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作者：
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作者：
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5.3
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Chen T;Li M;Zhang R;Wang H
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Wang H
影响因子：
168.9
作者：
Field, John K.;Oudkerk, Matthijs;Duffy, Stephen W.
通讯作者：
Duffy, Stephen W.