ID | 63856 |
フルテキストURL | |
著者 |
Ochi, Kosuke
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Suzawa, Ken
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
researchmap
Thu, Yin Min
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takatsu, Fumiaki
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsudaka, Shimpei
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Zhu, Yidan
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakata, Kentaro
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takeda, Tatsuaki
Departments of Pharmacy, Okayama University Hospital
ORCID
Shien, Kazuhiko
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Yamamoto, Hiromasa
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Okazaki, Mikio
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sugimoto, Seiichiro
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Shien, Tadahiko
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Okamoto, Yoshiharu
Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University
Tomida, Shuta
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Kaken ID
researchmap
Toyooka, Shinichi
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
|
抄録 | Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction.
|
キーワード | cancer-associated fibroblast
drug resistance
tranilast
|
発行日 | 2022-07-24
|
出版物タイトル |
Cancer Science
|
巻 | 2022巻
|
出版者 | Wiley
|
ISSN | 1347-9032
|
資料タイプ |
学術雑誌論文
|
言語 |
英語
|
OAI-PMH Set |
岡山大学
|
著作権者 | © 2022 The Authors.
|
論文のバージョン | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1111/cas.15502
|
ライセンス | https://creativecommons.org/licenses/by-nc/4.0/
|