Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

Lung cancer is the leading cause of cancer death worldwide. Cisplatin is the major DNA-damaging anticancer drug that cross-links the DNA in cancer cells, but many patients inevitably develop resistance with treatment. Identification of a cisplatin sensitizer might postpone or even reverse the develo...

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Autores principales:	Hefei Li, Yushan Zhang, Xiaomei Lan, Jianhua Yu, Changshuang Yang, Zhijian Sun, Ping Kang, Yi Han, Daping Yu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	lung cancer patient-derived organoid halofuginone PI3K/AKT MAPK Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/de72a317bcf34a199a69572a0f396bee
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spelling	oai:doaj.org-article:de72a317bcf34a199a69572a0f396bee2021-11-30T18:43:41ZHalofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways2296-634X10.3389/fcell.2021.773048https://doaj.org/article/de72a317bcf34a199a69572a0f396bee2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.773048/fullhttps://doaj.org/toc/2296-634XLung cancer is the leading cause of cancer death worldwide. Cisplatin is the major DNA-damaging anticancer drug that cross-links the DNA in cancer cells, but many patients inevitably develop resistance with treatment. Identification of a cisplatin sensitizer might postpone or even reverse the development of cisplatin resistance. Halofuginone (HF), a natural small molecule isolated from Dichroa febrifuga, has been found to play an antitumor role. In this study, we found that HF inhibited the proliferation, induced G0/G1 phase arrest, and promoted apoptosis in lung cancer cells in a dose-dependent manner. To explore the underlying mechanism of this antitumor effect of halofuginone, we performed RNA sequencing to profile transcriptomes of NSCLC cells treated with or without halofuginone. Gene expression profiling and KEGG analysis indicated that PI3K/AKT and MAPK signaling pathways were top-ranked pathways affected by halofuginone. Moreover, combination of cisplatin and HF revealed that HF could sensitize the cisplatin-resistant patient-derived lung cancer organoids and lung cancer cells to cisplatin treatment. Taken together, this study identified HF as a cisplatin sensitizer and a dual pathway inhibitor, which might provide a new strategy to improve prognosis of patients with cisplatin-resistant lung cancer.Hefei LiYushan ZhangXiaomei LanJianhua YuChangshuang YangZhijian SunPing KangYi HanDaping YuFrontiers Media S.A.articlelung cancerpatient-derived organoidhalofuginonePI3K/AKTMAPKBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung cancer patient-derived organoid halofuginone PI3K/AKT MAPK Biology (General) QH301-705.5
spellingShingle	lung cancer patient-derived organoid halofuginone PI3K/AKT MAPK Biology (General) QH301-705.5 Hefei Li Yushan Zhang Xiaomei Lan Jianhua Yu Changshuang Yang Zhijian Sun Ping Kang Yi Han Daping Yu Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
description	Lung cancer is the leading cause of cancer death worldwide. Cisplatin is the major DNA-damaging anticancer drug that cross-links the DNA in cancer cells, but many patients inevitably develop resistance with treatment. Identification of a cisplatin sensitizer might postpone or even reverse the development of cisplatin resistance. Halofuginone (HF), a natural small molecule isolated from Dichroa febrifuga, has been found to play an antitumor role. In this study, we found that HF inhibited the proliferation, induced G0/G1 phase arrest, and promoted apoptosis in lung cancer cells in a dose-dependent manner. To explore the underlying mechanism of this antitumor effect of halofuginone, we performed RNA sequencing to profile transcriptomes of NSCLC cells treated with or without halofuginone. Gene expression profiling and KEGG analysis indicated that PI3K/AKT and MAPK signaling pathways were top-ranked pathways affected by halofuginone. Moreover, combination of cisplatin and HF revealed that HF could sensitize the cisplatin-resistant patient-derived lung cancer organoids and lung cancer cells to cisplatin treatment. Taken together, this study identified HF as a cisplatin sensitizer and a dual pathway inhibitor, which might provide a new strategy to improve prognosis of patients with cisplatin-resistant lung cancer.
format	article
author	Hefei Li Yushan Zhang Xiaomei Lan Jianhua Yu Changshuang Yang Zhijian Sun Ping Kang Yi Han Daping Yu
author_facet	Hefei Li Yushan Zhang Xiaomei Lan Jianhua Yu Changshuang Yang Zhijian Sun Ping Kang Yi Han Daping Yu
author_sort	Hefei Li
title	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
title_short	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
title_full	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
title_fullStr	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
title_full_unstemmed	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
title_sort	halofuginone sensitizes lung cancer organoids to cisplatin via suppressing pi3k/akt and mapk signaling pathways
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/de72a317bcf34a199a69572a0f396bee
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Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

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