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Characterization of Cisplatin Effects in Lenvatinib-resistant Hepatocellular Carcinoma Cells

Sae Hamaya¹, Shintaro Fujihara¹, Hisakazu Iwama²

¹Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Anticancer Research

|February 27, 2022

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.

Keywords:

Hepatocellular carcinoma cell cycle cisplatin lenvatinib resistance microRNA

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