Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

Abstract 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...

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Autores principales:	Jing Du, Weiwei Chen, Lijuan Yang, Juanjuan Dai, Jiwei Guo, Yan Wu, Kaikai Gong, Jian Zhang, Ning Yu, Zhen Xie, Sichuan Xi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3284c0a2a41c4210bf423c354c810d0c
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spelling	oai:doaj.org-article:3284c0a2a41c4210bf423c354c810d0c2021-12-02T16:06:56ZDisruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment10.1038/s41598-017-02063-x2045-2322https://doaj.org/article/3284c0a2a41c4210bf423c354c810d0c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02063-xhttps://doaj.org/toc/2045-2322Abstract 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.Jing DuWeiwei ChenLijuan YangJuanjuan DaiJiwei GuoYan WuKaikai GongJian ZhangNing YuZhen XieSichuan XiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Du Weiwei Chen Lijuan Yang Juanjuan Dai Jiwei Guo Yan Wu Kaikai Gong Jian Zhang Ning Yu Zhen Xie Sichuan Xi Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment
description	Abstract 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	article
author	Jing Du Weiwei Chen Lijuan Yang Juanjuan Dai Jiwei Guo Yan Wu Kaikai Gong Jian Zhang Ning Yu Zhen Xie Sichuan Xi
author_facet	Jing Du Weiwei Chen Lijuan Yang Juanjuan Dai Jiwei Guo Yan Wu Kaikai Gong Jian Zhang Ning Yu Zhen Xie Sichuan Xi
author_sort	Jing Du
title	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_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_sort	disruption of shh signaling cascade by sbe attenuates lung cancer progression and sensitizes ddp treatment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3284c0a2a41c4210bf423c354c810d0c
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Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

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