HIF‐1 Inhibitors for Cancer Therapy

Anti-Tumor Drug-Loaded Oxygen Nanobubbles for the Degradation of HIF-1α and the Upregulation of Reactive Oxygen Species in Tumor Cells

“…We previously reported that the exposure of tumor cells to hypoxic conditions upregulates and stabilizes HIF-1α, while ONBs are effective in reversing hypoxia and downregulating HIF-1α [38]. The overexpression and stabilization of HIF-1α have been associated with resistance to Dox by many researchers [13,14,15,16,17,20,83,84,85,86]. In the current study, cells treated under hypoxic conditions were more resistant to free Dox, but were effectively killed by Dox/ONB conjugates.…”

“…Tumors under hypoxic conditions exhibit higher resistance to chemotherapy, radiotherapy, and photodynamic therapy [6,8,9]. Hypoxic conditions stabilize hypoxia-inducible factor-1 alpha (HIF-1α) protein, which has been reported to be a cause of tumor resistance to therapeutic mechanisms [7,10,11,12,13,14,15,16,17,18]. Within tumor cells, HIF-1α has been associated with a shift toward anaerobic metabolism and the expression of numerous genes involved in angiogenesis, apoptosis, pH regulation, and cellular differentiation.…”