Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways

Caihong Ye; Mengqi Wei; Huakun Huang; Yuping Wang; Lulu Zhang; Chunmei Yang; Yanran Huang; Jinyong Luo

doi:10.1515/hsz-2022-0148

Article

Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways

Caihong Ye , Mengqi Wei , Huakun Huang , Yuping Wang , Lulu Zhang , Chunmei Yang , Yanran Huang and Jinyong Luo

Published/Copyright: August 10, 2022

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From the journal Biological Chemistry Volume 403 Issue 10

Abstract

Osteosarcoma (OS) is the most prevalent malignant bone tumor with poor prognosis. Developing new drugs for the chemotherapy of OS has been a focal point and a major obstacle of OS treatment. Nitazoxanide (NTZ), a conventional anti-parasitic agent, has got increasingly noticed because of its favorable antitumor potential. Herein, we investigated the effect of NTZ on human OS cells in vitro and in vivo. The results obtained in vitro showed that NTZ inhibited the proliferation, migration and invasion, arrested cell cycle at G1 phase, while induced apoptosis of OS cells. Mechanistically, NTZ suppressed the activity of AKT/mTOR and Wnt/β-catenin signaling pathways of OS cells. Consistent with the results in vitro, orthotopic implantation model of 143B OS cells further confirmed that NTZ inhibited OS cells growth and lung metastasis in vivo. Notably, NTZ caused no apparent damage to normal cells/tissues. In conclusion, NTZ may inhibit tumor growth and metastasis of human OS cells through suppressing AKT/mTOR and Wnt/β-catenin signaling pathways.

Keywords: apoptosis; metastasis; osteosarcoma; proliferation; signaling pathways

Corresponding author: Jinyong Luo, Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, P.R. China, E-mail: luojinyong@cqmu.edu.cn

Caihong Ye and Mengqi Wei contributed equally to this work.

Funding source: the Natural Science Foundation Project of Chongqing Science and Technology Commission There is no funder DOI

Award Identifier / Grant number: cstc2017jcyjAX0196

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by the Natural Science Foundation Project of Chongqing Science and Technology Commission (no. cstc2017jcyjAX0196).
Conflict of interest statement: The authors declare that they have no competing interests.

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Received: 2022-03-25

Accepted: 2022-06-30

Published Online: 2022-08-10

Published in Print: 2022-09-27

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Keywords for this article

apoptosis; metastasis; osteosarcoma; proliferation; signaling pathways