Exploratory transcriptomics and <i>in vivo</i> analyses of suramin in tongue squamous cell carcinoma

Suramin, an anti-trypanosomal agent, has gained attention for its potential anticancer activity, partly through the modulation of RNA-binding proteins such as HuR. However, its genome-wide transcriptomic effects in oral squamous cell carcinoma remain unclear. In the present study, RNA-sequencing was performed on suramin-treated HSC-3 cells, followed by enrichment, network and transcription factor analyses. <i>In vivo</i> validation was conducted in an orthotopic xenograft model using luciferase-labeled HSC-3 cells. Suramin was administered intraperitoneally at a dose of 20 mg/kg, twice weekly. Transcriptomic profiling revealed broad downregulation of genes governing cell cycle progression, chromatin organization and DNA damage response, including mitotic regulators such as G₂/M regulators <i>CCNB1</i>, <i>CDC20</i> and <i>AURKA</i>, and their upstream transcription factors <i>FOXM1</i> and <i>MYBL2</i>. By contrast, genes associated with extracellular matrix remodeling (the MMP family and <i>TIMP3</i>) and stress or immune responses (<i>TXNIP</i> and <i>TNFSF10</i>) were upregulated. Functional enrichment confirmed the suppression of proliferative programs with the concurrent activation of tumor-suppressive microenvironmental responses. <i>In vivo</i>, suramin-treated mice exhibited lower tumor growth compared with that in the control group, although the difference was not statistically significant (P=0.18). Effect size estimates were relatively large for both the group effect (partial η²=0.20) and the time x group interaction (partial η²=0.24), suggesting that the study may have been underpowered to detect this difference statistically. In conclusion, the present exploratory study suggests that suramin exerts a dual antitumor effect on tongue squamous cell carcinoma by suppressing proliferative transcriptional programs, and modulating extracellular and stress response pathways, providing a basis for future studies to further elucidate its therapeutic relevance.