RRC ID 71618
Author Hamaya S, Fujihara S, Iwama H, Fujita K, Shi T, Nakabayashi R, Mizuo T, Takuma K, Nakahara M, Oura K, Tadokoro T, Mimura S, Tani J, Morishita A, Kobara H, Ono M, Himoto T, Masaki T.
Title Characterization of Cisplatin Effects in Lenvatinib-resistant Hepatocellular Carcinoma Cells.
Journal Anticancer Res
Abstract BACKGROUND/AIM: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: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: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: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.
Volume 42(3)
Pages 1263-1275
Published 2022-3-1
DOI 10.21873/anticanres.15593
PII 42/3/1263
PMID 35220216
MeSH Animals Antineoplastic Agents / pharmacology* Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology 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* Liver Neoplasms / genetics Liver Neoplasms / metabolism Liver Neoplasms / pathology Mice, Inbred BALB C Mice, Nude MicroRNAs / genetics MicroRNAs / metabolism Phenylurea Compounds / pharmacology* Protein Kinase Inhibitors / pharmacology* Quinolines / pharmacology* Signal Transduction Tumor Burden Xenograft Model Antitumor Assays
IF 1.994
Human and Animal Cells Li-7(RCB1941)