Ethacrynic acid suppresses B7-H4 expression involved in epithelial-mesenchymal transition of lung adenocarcinoma cells via inhibiting STAT3 pathway.

Animals Mice Transforming Growth Factor beta1 / metabolism Ethacrynic Acid / pharmacology Epithelial-Mesenchymal Transition Cell Line, Tumor Cell Movement Adenocarcinoma of Lung Lung Neoplasms / drug therapy
B7-H4 Epithelial-mesenchymal transition Ethacrynic acid Lun cancer STAT3

Journal

Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032

Informations de publication

Date de publication:
06 2023
Historique:
received: 07 01 2023
revised: 26 03 2023
accepted: 28 03 2023
medline: 22 5 2023
pubmed: 6 4 2023
entrez: 5 4 2023
Statut: ppublish

Résumé

Lung cancer is characterized by high incidence and mortality. 90% of cancer deaths are caused by metastases. The epithelial-mesenchymal transition (EMT) process in cancer cells is a prerequisite for the metastatic process. Ethacrynic acid (ECA) is a loop diuretic that inhibits the EMT process in lung cancer cells. EMT has been related to the tumour immunemicroenvironment. However, the effect of ECA on immune checkpoint molecules in the context of cancer has not been fully identified. In the present study, we found that sphingosylphosphorylcholine (SPC) and TGF-β1, awell-known EMT inducer, induced the expression of B7-H4 in lung cancer cells. We also investigated the involvement of B7-H4 in the SPC-induced EMT process. Knockdown of B7-H4 suppressed SPC-induced EMT, while B7-H4 overexpression enhanced EMT of lung cancer cells. ECA inhibited SPC/TGF-β1-induced B7-H4 expression via suppression of STAT3 activation. Moreover, ECA inhibits the colonization of mice lung by tail vein-injected LLC1 cells. ECA-treated mice increased the CD4-positive T cells in lung tumour tissues. In summary, these results suggested that ECA inhibits B7-H4 expression via STAT3 inhibition, leading to SPC/TGF-β1-induced EMT. Therefore, ECA might be an immune oncological drug for B7-H4-positive cancer, especially lung cancer.

Identifiants

DOI: 10.1016/j.bcp.2023.115537 PMID: 37019184
pubmed: 37019184
pii: S0006-2952(23)00128-4
doi: 10.1016/j.bcp.2023.115537
pii:
doi:

Substances chimiques

Transforming Growth Factor beta1 0
Ethacrynic Acid M5DP350VZV

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

115537

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Lu Yu (L)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Hyun Ji Kim (H)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Boram Kim (B)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Hyung Jung Byun (H)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Tuan Minh Nguyen (T)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Eun Ji Kim (E)

Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.

Hiu Huy Phùng (H)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Ye Hyeon Kim (Y)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Mostafizur Rahman (M)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Ji Yun Jang (J)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea; National Cancer Center, Goyang 10408, Korea.

Seung Bae Rho (S)

National Cancer Center, Goyang 10408, Korea.

Gyeoung Jin Kang (G)

Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.

Ho Lee (H)

National Cancer Center, Goyang 10408, Korea.

Kyeong Lee (K)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Hyo Kyung Han (H)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea.

Mi Kyung Park (M)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea; National Cancer Center, Goyang 10408, Korea. Electronic address: mkpark@ncc.re.kr.

Chang Hoon Lee (C)

BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul 04620, Korea. Electronic address: uatheone@dongguk.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Facteur de croissance transformant bêta › Facteur de croissance transformant bêta-1 › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Hydroxyacides › Glycolates › Phénoxy-acétates › Acide étacrynique › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transdifférenciation cellulaire › Transition épithélio-mésenchymateuse › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs du thorax › Adénocarcinome pulmonaire › Ethacrynic acid suppresses B7-H4 expression...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Ethacrynic acid suppresses B7-H4 expression...