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Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis
BACKGROUND: Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC. METHODS: Cell function tests...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829511/ https://www.ncbi.nlm.nih.gov/pubmed/33505963 http://dx.doi.org/10.3389/fcell.2020.605184 |
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author | Zheng, Dandan Zhu, Yu Shen, Yili Xiao, Sisi Yang, Lehe Xiang, Youqun Dai, Xuanxuan Hu, Wanle Zhou, Bin Liu, Zhiguo Zhao, Haiyang Zhao, Chengguang Huang, Xiaoying Wang, Liangxing |
author_facet | Zheng, Dandan Zhu, Yu Shen, Yili Xiao, Sisi Yang, Lehe Xiang, Youqun Dai, Xuanxuan Hu, Wanle Zhou, Bin Liu, Zhiguo Zhao, Haiyang Zhao, Chengguang Huang, Xiaoying Wang, Liangxing |
author_sort | Zheng, Dandan |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC. METHODS: Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice. RESULTS: Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model. CONCLUSION: The results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy. |
format | Online Article Text |
id | pubmed-7829511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78295112021-01-26 Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis Zheng, Dandan Zhu, Yu Shen, Yili Xiao, Sisi Yang, Lehe Xiang, Youqun Dai, Xuanxuan Hu, Wanle Zhou, Bin Liu, Zhiguo Zhao, Haiyang Zhao, Chengguang Huang, Xiaoying Wang, Liangxing Front Cell Dev Biol Cell and Developmental Biology BACKGROUND: Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC. METHODS: Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice. RESULTS: Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model. CONCLUSION: The results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7829511/ /pubmed/33505963 http://dx.doi.org/10.3389/fcell.2020.605184 Text en Copyright © 2021 Zheng, Zhu, Shen, Xiao, Yang, Xiang, Dai, Hu, Zhou, Liu, Zhao, Zhao, Huang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Zheng, Dandan Zhu, Yu Shen, Yili Xiao, Sisi Yang, Lehe Xiang, Youqun Dai, Xuanxuan Hu, Wanle Zhou, Bin Liu, Zhiguo Zhao, Haiyang Zhao, Chengguang Huang, Xiaoying Wang, Liangxing Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title | Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title_full | Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title_fullStr | Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title_full_unstemmed | Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title_short | Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis |
title_sort | cynaropicrin shows antitumor progression potential in colorectal cancer through mediation of the lifr/stats axis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829511/ https://www.ncbi.nlm.nih.gov/pubmed/33505963 http://dx.doi.org/10.3389/fcell.2020.605184 |
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