Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model

Abstract Although conventional chemoradiotherapy is effective for most anal squamous cell carcinoma (ASCC) patients, HPV-negative ASCC patients respond poorly to this treatment and new therapeutic approach is required. Our group has previously established an HPV-negative ASCC mouse model and demonst...

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Autores principales:	Lin-Lin Bu, Yi-Cun Li, Guang-Tao Yu, Jian-Feng Liu, Wei-Wei Deng, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb4ba309a10049e4a9ed6449710f706e
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spelling	oai:doaj.org-article:cb4ba309a10049e4a9ed6449710f706e2021-12-02T12:30:18ZTargeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model10.1038/s41598-017-06643-92045-2322https://doaj.org/article/cb4ba309a10049e4a9ed6449710f706e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06643-9https://doaj.org/toc/2045-2322Abstract Although conventional chemoradiotherapy is effective for most anal squamous cell carcinoma (ASCC) patients, HPV-negative ASCC patients respond poorly to this treatment and new therapeutic approach is required. Our group has previously established an HPV-negative ASCC mouse model and demonstrated that signal transducer and activation of transcription 3 (STAT3) is hyper-activated in the model. Here, we show that in vivo inhibition of STAT3 by S3I-201 effectively delays tumor growth in ASCC mouse model indicated by significantly smaller tumor size and burden in the treatment group compared with control group at the same point. Further analysis shows that survivin and Ki67, important biomarkers for tumor cell survival and proliferation, are significantly reduced after S3I-201 treatment. Additionally, flow cytometry and immunohistofluorescent assays reveal decreased Myeloid-derived suppressor cell (MDSC) and tumor-associated macrophage (TAM) populations in the S3I-201 treatment group, which indicates a reversion of the immunosuppressive environment, unraveling the potential role for S3I-201 in immunosuppression in ASCC. Together these results for the first time demonstrated the anti-tumor effects of STAT3 inhibitor S3I-201 in HPV-negative ASCC mouse model and its multiple effects on cancer cells and immune system. Thus we conclude that S3I-201 may be a novel therapeutic approach for HPV-negative ASCC patients.Lin-Lin BuYi-Cun LiGuang-Tao YuJian-Feng LiuWei-Wei DengWen-Feng ZhangLu ZhangZhi-Jun SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lin-Lin Bu Yi-Cun Li Guang-Tao Yu Jian-Feng Liu Wei-Wei Deng Wen-Feng Zhang Lu Zhang Zhi-Jun Sun Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
description	Abstract Although conventional chemoradiotherapy is effective for most anal squamous cell carcinoma (ASCC) patients, HPV-negative ASCC patients respond poorly to this treatment and new therapeutic approach is required. Our group has previously established an HPV-negative ASCC mouse model and demonstrated that signal transducer and activation of transcription 3 (STAT3) is hyper-activated in the model. Here, we show that in vivo inhibition of STAT3 by S3I-201 effectively delays tumor growth in ASCC mouse model indicated by significantly smaller tumor size and burden in the treatment group compared with control group at the same point. Further analysis shows that survivin and Ki67, important biomarkers for tumor cell survival and proliferation, are significantly reduced after S3I-201 treatment. Additionally, flow cytometry and immunohistofluorescent assays reveal decreased Myeloid-derived suppressor cell (MDSC) and tumor-associated macrophage (TAM) populations in the S3I-201 treatment group, which indicates a reversion of the immunosuppressive environment, unraveling the potential role for S3I-201 in immunosuppression in ASCC. Together these results for the first time demonstrated the anti-tumor effects of STAT3 inhibitor S3I-201 in HPV-negative ASCC mouse model and its multiple effects on cancer cells and immune system. Thus we conclude that S3I-201 may be a novel therapeutic approach for HPV-negative ASCC patients.
format	article
author	Lin-Lin Bu Yi-Cun Li Guang-Tao Yu Jian-Feng Liu Wei-Wei Deng Wen-Feng Zhang Lu Zhang Zhi-Jun Sun
author_facet	Lin-Lin Bu Yi-Cun Li Guang-Tao Yu Jian-Feng Liu Wei-Wei Deng Wen-Feng Zhang Lu Zhang Zhi-Jun Sun
author_sort	Lin-Lin Bu
title	Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
title_short	Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
title_full	Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
title_fullStr	Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
title_full_unstemmed	Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model
title_sort	targeting phosphorylation of stat3 delays tumor growth in hpv-negative anal squamous cell carcinoma mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cb4ba309a10049e4a9ed6449710f706e
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Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model

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