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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...

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Autores principales: Du, Jing, Chen, Weiwei, Yang, Lijuan, Dai, Juanjuan, Guo, Jiwei, Wu, Yan, Gong, Kaikai, Zhang, Jian, Yu, Ning, Xie, Zhen, Xi, Sichuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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.
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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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