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Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression

The aim of this study was to: (a) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5‐fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and (b) identify potential alternative agents for pa...

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Autores principales: Zhao, Tong‐Chao, Zhou, Zhi‐Hang, Ju, Wu‐Tong, Liang, Si‐Yuan, Tang, Xiao, Zhu, Dong‐Wang, Zhang, Zhi‐Yuan, Zhong, Lai‐Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819339/
https://www.ncbi.nlm.nih.gov/pubmed/34826159
http://dx.doi.org/10.1111/cas.15218
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author Zhao, Tong‐Chao
Zhou, Zhi‐Hang
Ju, Wu‐Tong
Liang, Si‐Yuan
Tang, Xiao
Zhu, Dong‐Wang
Zhang, Zhi‐Yuan
Zhong, Lai‐Ping
author_facet Zhao, Tong‐Chao
Zhou, Zhi‐Hang
Ju, Wu‐Tong
Liang, Si‐Yuan
Tang, Xiao
Zhu, Dong‐Wang
Zhang, Zhi‐Yuan
Zhong, Lai‐Ping
author_sort Zhao, Tong‐Chao
collection PubMed
description The aim of this study was to: (a) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5‐fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and (b) identify potential alternative agents for patients who might not benefit from inductive TPF chemotherapy. The results indicated that OSCC cells overexpressing GDF15 were sensitive to TPF through a caspase‐9‐dependent pathway both in vitro and in vivo. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential GDF15‐binding protein, which was verified by coimmunoprecipitation. Growth differentiation factor 15 overexpression promoted OSCC cell proliferation through erbB2 phosphorylation, as well as downstream AKT and Erk signaling pathways. When GDF15 expression was blocked, the phosphorylation of both the erbB2 and AKT/Erk pathways was downregulated. When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI‐1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). Thus, GDF15‐overexpressing OSCC tumors are sensitive to TPF chemoagents through caspase‐9‐dependent pathways. Growth differentiation factor 15 overexpression promotes OSCC proliferation through erbB2 phosphorylation. Thus, ErbB2 inhibitors could represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression.
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spelling pubmed-88193392022-02-11 Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression Zhao, Tong‐Chao Zhou, Zhi‐Hang Ju, Wu‐Tong Liang, Si‐Yuan Tang, Xiao Zhu, Dong‐Wang Zhang, Zhi‐Yuan Zhong, Lai‐Ping Cancer Sci Original Articles The aim of this study was to: (a) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5‐fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and (b) identify potential alternative agents for patients who might not benefit from inductive TPF chemotherapy. The results indicated that OSCC cells overexpressing GDF15 were sensitive to TPF through a caspase‐9‐dependent pathway both in vitro and in vivo. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential GDF15‐binding protein, which was verified by coimmunoprecipitation. Growth differentiation factor 15 overexpression promoted OSCC cell proliferation through erbB2 phosphorylation, as well as downstream AKT and Erk signaling pathways. When GDF15 expression was blocked, the phosphorylation of both the erbB2 and AKT/Erk pathways was downregulated. When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI‐1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). Thus, GDF15‐overexpressing OSCC tumors are sensitive to TPF chemoagents through caspase‐9‐dependent pathways. Growth differentiation factor 15 overexpression promotes OSCC proliferation through erbB2 phosphorylation. Thus, ErbB2 inhibitors could represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression. John Wiley and Sons Inc. 2021-12-20 2022-02 /pmc/articles/PMC8819339/ /pubmed/34826159 http://dx.doi.org/10.1111/cas.15218 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Zhao, Tong‐Chao
Zhou, Zhi‐Hang
Ju, Wu‐Tong
Liang, Si‐Yuan
Tang, Xiao
Zhu, Dong‐Wang
Zhang, Zhi‐Yuan
Zhong, Lai‐Ping
Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title_full Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title_fullStr Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title_full_unstemmed Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title_short Mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression
title_sort mechanism of sensitivity to cisplatin, docetaxel, and 5‐fluorouracil chemoagents and potential erbb2 alternatives in oral cancer with growth differentiation factor 15 overexpression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819339/
https://www.ncbi.nlm.nih.gov/pubmed/34826159
http://dx.doi.org/10.1111/cas.15218
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