Hypoxia Mediated Glycoprotein-170 Expression: Role in Cancer Cells Chemo Resistance

Abstract

Solid tumors frequently grow in a micro-environment characterized by hypoxia (< 2% O 2 tension). This condition, together with the abnormal activation of specific oncogenic pathways, increases the activity of the hypoxia-inducible factor-1α (HIF-1α), a transcription factor that is known to control more than 200 genes involved in multiple cells process including in neo angiogenesis, apoptosis, metabolic rewiring, metastasis and drug resistance. HIF-1α induces the expression of P-gp, protein that acts as an energy-dependent pump to transport cytotoxic agents out of the cells, and its expression is correlated with resistance to multiple drugs in several kinds of cancer. Hypoxia induces chemoresistance via induction of P-gp. In this review, we discuss the multiple and interconnected circuitries that link hypoxic environment and drug resistance focus in the regulation of P-gp. We believe that pharmacological inhibitors of HIF-1α and modulators of P-gp, although characterized by low specificity and anti-cancer efficacy when used as single agents, may be considered as chemosensitizers against hypoxic and chemo refractory tumors in the near future.