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Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment
Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the spec...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432500/ https://www.ncbi.nlm.nih.gov/pubmed/28507311 http://dx.doi.org/10.1038/s41598-017-02063-x |
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author | Du, Jing Chen, Weiwei Yang, Lijuan Dai, Juanjuan Guo, Jiwei Wu, Yan Gong, Kaikai Zhang, Jian Yu, Ning Xie, Zhen Xi, Sichuan |
author_facet | Du, Jing Chen, Weiwei Yang, Lijuan Dai, Juanjuan Guo, Jiwei Wu, Yan Gong, Kaikai Zhang, Jian Yu, Ning Xie, Zhen Xi, Sichuan |
author_sort | Du, Jing |
collection | PubMed |
description | Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells. This study revealed that SBE specifically repressed SHH signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis via arresting cell cycle progression. We also found that SBE significantly sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH components in vitro and in vivo. Mechanistic investigations indicated that SBE transcriptionally and specifically downregulated SMO and consequently attenuated the activities of GLI1 and its downstream targets in SHH signaling pathway, which interacted with cell cycle checkpoint enzymes to arrest cell cycle progression and lead to cellular growth inhibition and migration blockade. Collectively, our results suggest SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. |
format | Online Article Text |
id | pubmed-5432500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54325002017-05-16 Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment Du, Jing Chen, Weiwei Yang, Lijuan Dai, Juanjuan Guo, Jiwei Wu, Yan Gong, Kaikai Zhang, Jian Yu, Ning Xie, Zhen Xi, Sichuan Sci Rep Article Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells. This study revealed that SBE specifically repressed SHH signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis via arresting cell cycle progression. We also found that SBE significantly sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH components in vitro and in vivo. Mechanistic investigations indicated that SBE transcriptionally and specifically downregulated SMO and consequently attenuated the activities of GLI1 and its downstream targets in SHH signaling pathway, which interacted with cell cycle checkpoint enzymes to arrest cell cycle progression and lead to cellular growth inhibition and migration blockade. Collectively, our results suggest SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. Nature Publishing Group UK 2017-05-15 /pmc/articles/PMC5432500/ /pubmed/28507311 http://dx.doi.org/10.1038/s41598-017-02063-x Text en © The Author(s) 2017 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/. |
spellingShingle | Article Du, Jing Chen, Weiwei Yang, Lijuan Dai, Juanjuan Guo, Jiwei Wu, Yan Gong, Kaikai Zhang, Jian Yu, Ning Xie, Zhen Xi, Sichuan Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title | Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title_full | Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title_fullStr | Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title_full_unstemmed | Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title_short | Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment |
title_sort | disruption of shh signaling cascade by sbe attenuates lung cancer progression and sensitizes ddp treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432500/ https://www.ncbi.nlm.nih.gov/pubmed/28507311 http://dx.doi.org/10.1038/s41598-017-02063-x |
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