Effects of Hif-1α inhibition under hypoxic conditions on doxorubicin response in B16.F10 murine melanoma cells

Hipoxia inducible factor 1 (HIF-1) is major regulator of cellular adaptations to low oxygen concentrations, responsible for transcriptional programs that promote metabolic reprogramming, cell survival, and drug resistance. RNA sequencing was performed to characterize transcriptomic changes in B16.F10 murine melanoma cells cultured under 1% hypoxia following Hif-1α silencing and doxorubicin treatment. Differential gene expression analysis of the treatment group revealed extensive downregulation of metabolic pathways (glycolysis, oxidative phosphorylation, cholesterol homeostasis, and mTORC1 signaling). In parallel, genes associated with stress and cell death responses, including p38 MAPK signaling, p53 signaling, Notch signaling, and angiogenesis, were upregulated. Taken together, the treatment, promoted cell death and increased sensitivity to doxorubicin, supporting the potential of targeting hypoxia associated mechanisms to enhance therapeutic efficacy in hypoxic tumors.