Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Liu,Yueliang; Wang,Wenjuan; Xu,Jing; Li,Li; Dong,Qian; Shi,Qiong; Zuo,Guowei; Zhou,Lan; Weng,Yaguang; Tang,Min; He,Tongchuan; Luo,Jinyong

doi:10.3892/or.2013.2658

Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

Authors:
- Yueliang Liu
- Wenjuan Wang
- Jing Xu
- Li Li
- Qian Dong
- Qiong Shi
- Guowei Zuo
- Lan Zhou
- Yaguang Weng
- Min Tang
- Tongchuan He
- Jinyong Luo
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Affiliations: Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China, Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA
Published online on: August 5, 2013 https://doi.org/10.3892/or.2013.2658
Pages: 1723-1730

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Abstract

Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of dihydroartemisinin (DHA) on human OS cells and the possible molecular mechanisms involved. We demonstrated that DHA can inhibit proliferation, decrease migration, reduce invasion and induce apoptosis in human OS cells. Using an in vivo tumor animal model, we confirmed that DHA can prevent OS formation and maintain intact bone structure in athymic mice. In addition, we examined the possible molecular mechanisms mediating the function of DHA. We found that the total protein levels and transcriptional activity of β-catenin in OS cells are reduced by DHA treatment, and this may result from the increased catalytic activity of glycogen synthase kinase 3β (GSK3β). Moreover, the inhibitory effect of DHA on OS cells is reversed by overexpression of β-catenin, but is further enhanced by knockdown of β-catenin, respectively. Collectively, our results reveal that DHA can inhibit tumor growth of OS cells by inactivating Wnt/β-catenin signaling. Therefore, DHA is a promising chemotherapy agent in the treatment of human OS.

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