Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer

Zhou, Mo; Haga, Yuya; Nishimura, Akihide; Tanahashi, Suzuno; Higashisaka, Kazuma; Tsutsumi, Yasuo

doi:https://doi.org/10.1016/j.bbrc.2025.152107

Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer

Zhou, Mo; Haga, Yuya; Nishimura, Akihide et al.

Biochemical and Biophysical Research Communications, 2025, 775, 152107

Number of Access:17（2025-09-09 18:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102605

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Title	Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer
Creator	CreatorName Zhou, Mo
	NRID 1000030888863 1000030888863 ORCID 0000-0003-4148-2256 0000-0003-4148-2256 researchmap permalink 30888863 30888863 Scopus Author ID 57211023415 57211023415 CreatorName Haga, Yuya
	CreatorName Nishimura, Akihide
	CreatorName Tanahashi, Suzuno
	CreatorName Higashisaka, Kazuma
	NRID 1000050263306 1000050263306 researchmap permalink ytsutsumi ytsutsumi Scopus Author ID 7202474093 7202474093 CreatorName Tsutsumi, Yasuo
Subject	Cell cycle dynamics
	Drug tolerant persister cells (DTPs)
	EGFR-TKI
	Fucci imaging
	Non-small cell lung cancer (NSCLC)
Description	Zhou M., Haga Y., Nishimura A., et al. Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer. Biochemical and Biophysical Research Communications 775, 152107 (2025); https://doi.org/10.1016/j.bbrc.2025.152107.
Abstract	Molecular-targeted therapy remains effective in cancer treatment; however, drug resistance inevitably arises after prolonged administration for several years. Drug-tolerant persister cells (DTPs), which are subpopulations of cells derived from drug-sensitive cells that develop tolerance after short-term exposure (lasting days or weeks) to drugs, have gained substantial attention. However, the specific characteristics of DTPs remain unclear as they encompass a diverse cell population, although they generally exhibit low proliferative potential. Therefore, analysis of cell cycle fluctuations during and after the formation of DTPs is expected to elucidate DTPs characteristics and contribute to future therapies. Here, we introduced the Fucci probe into the PC9 cell line to create PC9-Fucci to observe dynamic cell cycle variations during and after the DTPs formation process. The results showed that during the formation of DTPs, the majority of cells showed red fluorescence and were arrested in the G1 phase, whereas a small number of S-phase cells showed green fluorescence. Furthermore, some cells proliferated after the DTPs phase under drug-free medium and drug-containing medium culture conditions. These results indicate cell cycle diversity, with the majority of cells exhibiting arrested cell cycle during the formation of DTPs, whereas others existed in the S phase. In addition, cell cycle diversity occurs not only in the process of DTPs formation but also in subsequent processes.
Publisher	Elsevier B.V.
Source Title	Biochemical and Biophysical Research Communications
Volume (Issue)	775
Page	152107
Date of Issued	2025-05-30
Language	English
Handle URL	https://hdl.handle.net/11094/102605
PISSN	0006291X
eISSN	10902104
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.bbrc.2025.152107
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Biochemical and Biophysical Research Communications. 2025, 775, p. 152107
DC.title	Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer
DC.creator	Zhou, Mo
	Haga, Yuya
	Nishimura, Akihide
	Tanahashi, Suzuno
	Higashisaka, Kazuma
	Tsutsumi, Yasuo
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-05-30
DC.identifier	https://doi.org/10.1016/j.bbrc.2025.152107
DC.subject	Cell cycle dynamics
	Drug tolerant persister cells (DTPs)
	EGFR-TKI
	Fucci imaging
	Non-small cell lung cancer (NSCLC)
DC.description	Zhou M., Haga Y., Nishimura A., et al. Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer. Biochemical and Biophysical Research Communications 775, 152107 (2025); https://doi.org/10.1016/j.bbrc.2025.152107.
DCTERMS.abstract	Molecular-targeted therapy remains effective in cancer treatment; however, drug resistance inevitably arises after prolonged administration for several years. Drug-tolerant persister cells (DTPs), which are subpopulations of cells derived from drug-sensitive cells that develop tolerance after short-term exposure (lasting days or weeks) to drugs, have gained substantial attention. However, the specific characteristics of DTPs remain unclear as they encompass a diverse cell population, although they generally exhibit low proliferative potential. Therefore, analysis of cell cycle fluctuations during and after the formation of DTPs is expected to elucidate DTPs characteristics and contribute to future therapies. Here, we introduced the Fucci probe into the PC9 cell line to create PC9-Fucci to observe dynamic cell cycle variations during and after the DTPs formation process. The results showed that during the formation of DTPs, the majority of cells showed red fluorescence and were arrested in the G1 phase, whereas a small number of S-phase cells showed green fluorescence. Furthermore, some cells proliferated after the DTPs phase under drug-free medium and drug-containing medium culture conditions. These results indicate cell cycle diversity, with the majority of cells exhibiting arrested cell cycle during the formation of DTPs, whereas others existed in the S phase. In addition, cell cycle diversity occurs not only in the process of DTPs formation but also in subsequent processes.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102605
citation_title	Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer
citation_author	Zhou, Mo
	Haga, Yuya
	Nishimura, Akihide
	Tanahashi, Suzuno
	Higashisaka, Kazuma
	Tsutsumi, Yasuo
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2025-05-30
citation_journal_title	Biochemical and Biophysical Research Communications
citation_volume	775
citation_firstpage	152107
citation_doi	https://doi.org/10.1016/j.bbrc.2025.152107
citation_public_url	https://hdl.handle.net/11094/102605

Cell cycle dynamics analysis of drug-tolerant persister cells in non-small cell lung cancer

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