ID | 62824 |
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Author |
Sun, Jingkai
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Lin, Wenfeng
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Li, Chaoming
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ueki, Hideo
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Xue, Ruizhi
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sadahira, Takuya
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hu, Hao
Laboratory of Medical Systems Biology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
Wada, Koichiro
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Li, Na
Laboratory of Medical Systems Biology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University
Liu, Chunxiao
Department of Urology, Zhujiang Hospital, Southern Medical University
Araki, Motoo
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Xu, Abai
Department of Urology, Zhujiang Hospital, Southern Medical University
Huang, Peng
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | Posaconazole (POS) is a novel antifungal agent, which has been repurposed as an anti-tumor drug for its potential inhibition of Hedgehog signaling pathway. Hedgehog pathway is reported to be abnormally activated in embryonal rhabdomyosarcoma (ERMS), this study aimed to reveal whether POS could inhibit Hedgehog signaling pathway in ERMS. Following POS treatment, XTT viability assay was used to determine the cell proliferation of ERMS cell lines. Protein changes related to Hedgehog signaling, cell cycle and autophagy were detected by Western blot. The cell cycle distribution was analyzed by flow cytometry. Moreover, a subcutaneous tumor mouse model of ERMS was established to assess the anti-tumor effect of POS. POS was found to inhibit tumor progression by inducing G0/G1 arrest and autophagy of RD, RMS-YM, and KYM-1 cells dose-dependently. Western blot demonstrated that POS downregulated the expressions of SMO, Gli1, c-Myc, CDK4, and CDK6, while upregulated the expressions of autophagy-related proteins. Immunofluorescence microscopy revealed a significant increase of LC3B puncta in POS-treated ERMS cells. Furthermore, POS treatment led to a significant inhibition of tumor growth in mice bearing ERMS. Our findings could provide a theoretical basis and have important clinical implications in developing POS as a promising agent against ERMS by targeting Hedgehog pathway.
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Keywords | Posaconazole
cell cycle
autophagy
rhabdomyosarcoma
hedgehog proteins
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Published Date | 2021-09-30
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Publication Title |
American Journal of Cancer Research
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Volume | volume11
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Issue | issue9
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Publisher | e-Century Publishing Corporation
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Start Page | 4528
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End Page | 4540
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ISSN | 2156-6976
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | AJCR (c)2021 e-Century Publishing Corp.
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File Version | publisher
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PubMed ID | |
Web of Science KeyUT | |
License | AJCR Copyright © 2021
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Citation | Sun J, Lin W, Li C, et al. Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy. Am J Cancer Res. 2021;11(9):4528-4540. Published 2021 Sep 15.
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