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Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual...

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Autores principales: Cao, Yaoquan, Tang, Haibo, Wang, Guohui, Li, Pengzhou, Song, Zhi, Li, Weizheng, Sun, Xulong, Zhong, Xiaoxiao, Yu, Qianqian, Zhu, Shaihong, Zhu, Liyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520088/
https://www.ncbi.nlm.nih.gov/pubmed/37749082
http://dx.doi.org/10.1038/s41420-023-01622-8
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author Cao, Yaoquan
Tang, Haibo
Wang, Guohui
Li, Pengzhou
Song, Zhi
Li, Weizheng
Sun, Xulong
Zhong, Xiaoxiao
Yu, Qianqian
Zhu, Shaihong
Zhu, Liyong
author_facet Cao, Yaoquan
Tang, Haibo
Wang, Guohui
Li, Pengzhou
Song, Zhi
Li, Weizheng
Sun, Xulong
Zhong, Xiaoxiao
Yu, Qianqian
Zhu, Shaihong
Zhu, Liyong
author_sort Cao, Yaoquan
collection PubMed
description The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.
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spelling pubmed-105200882023-09-27 Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer Cao, Yaoquan Tang, Haibo Wang, Guohui Li, Pengzhou Song, Zhi Li, Weizheng Sun, Xulong Zhong, Xiaoxiao Yu, Qianqian Zhu, Shaihong Zhu, Liyong Cell Death Discov Article The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance. Nature Publishing Group UK 2023-09-25 /pmc/articles/PMC10520088/ /pubmed/37749082 http://dx.doi.org/10.1038/s41420-023-01622-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cao, Yaoquan
Tang, Haibo
Wang, Guohui
Li, Pengzhou
Song, Zhi
Li, Weizheng
Sun, Xulong
Zhong, Xiaoxiao
Yu, Qianqian
Zhu, Shaihong
Zhu, Liyong
Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title_full Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title_fullStr Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title_full_unstemmed Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title_short Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
title_sort targeting survivin with tanshinone iia inhibits tumor growth and overcomes chemoresistance in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520088/
https://www.ncbi.nlm.nih.gov/pubmed/37749082
http://dx.doi.org/10.1038/s41420-023-01622-8
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