Characterization of Cisplatin Effects in Lenvatinib-resistant Hepatocellular Carcinoma Cells.
Animals
Antineoplastic Agents
/ pharmacology
Carcinoma, Hepatocellular
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cisplatin
/ pharmacology
Drug Resistance, Neoplasm
Female
G2 Phase Cell Cycle Checkpoints
/ drug effects
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms
/ drug therapy
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Phenylurea Compounds
/ pharmacology
Protein Kinase Inhibitors
/ pharmacology
Quinolines
/ pharmacology
Signal Transduction
Tumor Burden
Xenograft Model Antitumor Assays
Hepatocellular carcinoma
cell cycle
cisplatin
lenvatinib resistance
microRNA
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
09
12
2021
revised:
11
01
2022
accepted:
12
01
2022
entrez:
27
2
2022
pubmed:
28
2
2022
medline:
8
3
2022
Statut:
ppublish
Résumé
Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC). LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells. The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway. Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
METHODS
LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells.
RESULTS
RESULTS
The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway.
CONCLUSION
CONCLUSIONS
Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.
Identifiants
pubmed: 35220216
pii: 42/3/1263
doi: 10.21873/anticanres.15593
doi:
Substances chimiques
Antineoplastic Agents
0
MicroRNAs
0
Phenylurea Compounds
0
Protein Kinase Inhibitors
0
Quinolines
0
lenvatinib
EE083865G2
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1263-1275Informations de copyright
Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.