Cytochalasin H enhances sensitivity to gefitinib in non-small-cell lung cancer cells through inhibiting EGFR activation and PD-L1 expression.
Gefitinib
/ pharmacology
ErbB Receptors
/ metabolism
B7-H1 Antigen
/ metabolism
Humans
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Animals
Lung Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Mice
Cytochalasins
/ pharmacology
Xenograft Model Antitumor Assays
Antineoplastic Agents
/ pharmacology
Mice, Nude
Drug Resistance, Neoplasm
/ drug effects
A549 Cells
Cytochalasin H
EGFR
Gefitinib
JAK3-STAT
NSCLC
PD-L1
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
14
06
2024
accepted:
10
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
In our previous study, we have isolated cytochalasin H (CyH) from endophytic fungus derived from mangrove plant and found that CyH inhibited the proliferation of non-small cell lung cancer (NSCLC) cells. Recently, epidermal growth factor receptor (EGFR) activation and programmed cell death 1 ligand (PD-L1) expression have been demonstrated to mediate NSCLC resistance to gefitinib, first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI). Here, we further investigated the effect of CyH on EGFR activation, PD-L1 expression, and gefitinib sensitivity in NSCLC cell lines, A549 (wild-type EGFR), HCC827 (EGFR mutation), and NCI-H1975 (dual EGFR mutations and acquired gefitinib resistance) and animal model. Our results showed that CyH significantly inhibited EGFR activation and PD-L1 expression in NSCLC cells. Additionally, CyH dramatically promoted the inhibitory effect of gefitinib on the proliferation of A549 and HCC827 cells, and enhanced the sensitivity to gefitinib in NCI-H1975 cells. Moreover, CyH increased the inhibitory effect of gefitinib on EGFR activation and PD-L1 expression in HCC827 and NCI-H1975 cells. Animal experiments further demonstrated that CyH significantly promoted the inhibitory effect of gefitinib on the growth of NSCLC and the expression of Ki-67, p-EGFR, and PD-L1 in NCI-H1975 NSCLC xenograft tumors of nude mice. Furthermore, CyH inhibited the activation of JAK3/STAT signaling pathway. Taken together, our findings suggest that CyH promotes the sensitivity to gefitinib in NSCLC cells through the inhibition of EGFR activation and PD-L1 expression.
Identifiants
pubmed: 39455693
doi: 10.1038/s41598-024-76060-2
pii: 10.1038/s41598-024-76060-2
doi:
Substances chimiques
Gefitinib
S65743JHBS
ErbB Receptors
EC 2.7.10.1
B7-H1 Antigen
0
CD274 protein, human
0
Cytochalasins
0
EGFR protein, human
EC 2.7.10.1
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25276Subventions
Organisme : Guangdong Basic and Applied Basic Research Foundation
ID : 2023A1515010103
Organisme : Characteristic Innovation Project of Guangdong Province Ordinary University (Nature Science)
ID : 2022KTSCX048
Informations de copyright
© 2024. The Author(s).
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