ID | 62344 |
フルテキストURL | |
著者 |
Lin, Wenfeng
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sun, Jingkai
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
Xu, Naijin
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Wada, Koichiro
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
researchmap
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
ORCID
Kaken ID
publons
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Xu, Abai
Department of Urology, Zhujiang Hospital, Southern Medical University
Watanabe, Masami
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
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Nasu, Yasutomo
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
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Huang, Peng
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time-and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.
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キーワード | Urothelial bladder cancer
doxorubicin
cisplatin
chemoresistance
nitroxoline
STAT3
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発行日 | 2021-07-25
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出版物タイトル |
International Journal of Biological Sciences
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巻 | 17巻
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号 | 12号
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出版者 | Ivyspring International Publisher
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開始ページ | 3255
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終了ページ | 3267
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ISSN | 1449-2288
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The author(s).
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論文のバージョン | publisher
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DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.7150/ijbs.63125
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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助成機関名 |
文部科学省
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助成番号 | 17K11138
21K09371
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オープンアクセス(出版社) |
OA
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