Adipose-Derived Stem Cell-Conditioned Medium Enhances Aggressive Cellular Features in CoCl₂-Adapted Oral Squamous Cell Carcinoma Cells

Objective: The progression of oral squamous cell carcinoma (OSCC) is strongly influenced by hypoxia and signals derived from the tumor microenvironment. This study aimed to investigate the effects of adipose-derived stem cell-conditioned medium (ASC-CM) on CoCl₂-induced hypoxic UPCI-SCC-131 cells.Methods: Hypoxia induction was confirmed by significant upregulation of HIF1A and CA9 gene expression and increased Hif1α protein levels. The effects of ASC-CM on cell viability were assessed, and the expression of genes associated with cell survival and stress responses was analyzed by RT-qPCR. Intracellular reactive oxygen species (ROS) production, migratory capacity, spheroid formation, and sensitivity to cisplatin were also evaluated.Results: ASC-CM slightly reduced cell viability while markedly altering cellular behavior. RT-qPCR analysis revealed downregulation of the cell survival-related genes APAF1, CASP2, CASP9, and BAX, accompanied by increased BCL2 expression. In addition, the expression levels of HMOX1, CCL2, HIF1A, and CA9 were significantly increased, suggesting activation of oxidative stress- and survival-associated responses. Functionally, ASC-CM enhanced intracellular ROS production, increased migratory and spheroid formation capacity, and reduced sensitivity to cisplatin.Conclusion: These findings suggest that ASC-derived conditioned medium modulates oxidative stress- and cell survival-associated responses and influences several cellular behaviors associated with tumor progression in hypoxia-mimicking OSCC cells. The results further indicate that factors derived from the tumor microenvironment may contribute to the development of a more aggressive phenotype in hypoxic OSCC cells.