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

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.