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Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma

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Summary

Osteosarcoma is the most common primary malignancy of bone and characterized by an appendicular primary tumor with a high rate of metastasis to the lungs. Unfortunately, there is no effective strategy to treat osteosarcoma in current clinical practice. In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. The results of the antiproliferative activity in vitro showed that nifuroxazide inhibited cell proliferation of UMR106 and MG63 cells in a dose- and time-dependent manner. Interestingly, nifuroxazide showed low toxicity to non-tumor cells (HEK 293 T). In addition, ROS-mitochondrial mediated apoptosis was observed after treatment of nifuroxazide. Moreover, nifuroxazide could significantly inhibit osteosarcoma cells migration and invasion via p-Stat3, MMP-2 and MMP-9 mediated signaling pathway. Taken together, our results suggested that nifuroxazide could be a promising agent for osteosarcoma treatment by inhibiting cell proliferation, inducing cell apoptosis and impairing cell migration and invasion.

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Funding

This work was supported by the Support Program for Science and Technology of Sichuan Province (2017SZ0106).

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Authors and Affiliations

  1. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China

    Yi Luo & Chongqi Tu

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China

    Yi Luo, Aiping Fang, Chen Fan, Chenjuan Zeng, Tinghong Ye & Yongmei Xie

  3. Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan Province, 610064, People’s Republic of China

    Anqi Zeng

  4. School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610041, People’s Republic of China

    Linjiang Song

  5. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Healthy Science Center, Memphis, TN, 38163, USA

    Hao Chen

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  1. Yi Luo
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Correspondence to Yongmei Xie.

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Luo, Y., Zeng, A., Fang, A. et al. Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma. Invest New Drugs 37, 1006–1013 (2019). https://doi.org/10.1007/s10637-019-00724-4

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  • DOI: https://doi.org/10.1007/s10637-019-00724-4

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