期刊
ONCOTARGET
卷 7, 期 21, 页码 31413-31428出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8920
关键词
non-small-cell lung cancer; artemisinin; derivative; Wnt/beta-catenin
资金
- National Natural Science Foundation of China [81473410, 81503466]
- Science and Technology Project of Guangzhou City [201509010004]
- Guangdong Natural Science Foundation Province [2015AD030312012]
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/beta-catenin pathway, and Wnt5a siRNA, we found that ART, DHA, and ARTS could render tumor inhibition partially dependent on Wnt/beta-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 beta-catenin downregulation. In summary, our findings revealed that ART, DHA, and ARTS could suppress lung-tumor progression by inhibiting Wnt/beta-catenin pathway, thereby suggesting a novel target for ART, DHA, and ARTS in cancer treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据