A scheme to tackle the dilemma from hepatoma cells under doxorubicin-resistant surroundings: a brightness or a silhouette

Artificial Cells, Nanomedicine, and Biotechnology · Published 2026-07-21 · DOI 10.1080/21691401.2026.2694920

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Authors (6)

Ki-Kwang Oh, Goo-Hyun Kwon, Jung-A Eom, Kyeong Jin Lee, Dong Joon Kim, Ki-Tae Suk

Abstract

Background The aim of this study was to investigate key target(s), mechanism(s) from hepatoma cells in harsh doxorubicin-resistant conditions (DRCs) from GSE125180 datasets in GEO (Gene Expression Omnibus).Methods The identified components can be denoted as a brightness (therapeutic mark) or darkness (resistant mark) in DRCs. The protein-protein interaction (PPI) networks were assembled to identify the relationships between upregulated and downregulated genes via STRING, and R program.Results In the |log2 FC| > 1, and |log2 FC| > 2 subgroups, the uppermost target was a non-receptor tyrosine kinase (SRC) downregulated in DRCs, indicating that the dampened SRC is a therapeutic mark by doxorubicin (DOX). In contrast, in the |log2 FC| > 3 subgroup, the most significant target was Cluster of Differentiation 93 (CD93) upregulated in DRCs, suggesting that the overexpressed CD93 is a resistant mark in DRCs. Metoclopramide (MET) @ CD93 + DOX conformer is a highlighted capture to illuminate as combination therapy to overcome DRCs because MET is an inhibitor against CD93 as well as a non-competitive inhibitor on (MET @ CD93 + DOX) conformer.Conclusions These findings provide a mechanistic rationale for repurposing MET as an adjuvant agent to enhance therapeutic efficacy and overcome drug resistance in combination treatment strategies.

Abstract from DOAJ. Public domain (CC0 1.0).

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Publication details

Year
2026

Citation

Oh, K., Kwon, G., Eom, J., et al. (2026). A scheme to tackle the dilemma from hepatoma cells under doxorubicin-resistant surroundings: a brightness or a silhouette. Artificial Cells, Nanomedicine, and Biotechnology. https://doi.org/10.1080/21691401.2026.2694920

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