Fig. 7
From: Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Hypoxia enhances tumor chemotherapy resistance. IL-6 stimulates HIF-1α expression, which increases PGP expression through upregulation of miR-27a. Chemotherapeutic agents are transported by HIF-1α-induced intracellular MRP1 and excreted from cells via PGP and BCRP. HIF-1α induces OLFM4 to enhance cancer cell chemoresistance. HIF-1α enhances chemotherapeutic resistance in cancer cells by promoting PKM1, enhancing mitochondrial OXPHOS. Under hypoxic conditions, cancer cells induce enhanced autophagy and inhibit the chemotherapeutic drug-induced BNIP3 death pathway to resist drug toxicity. HIF-1α synergizes with TGF-β to promote GLI2 expression through SMAD3, inducing cancer cell stemness and chemoresistance. HIF-2α upregulation promotes the ability of hypoxic cancer cells to resist drug toxicity by activating the TGF-α/EGFR pathway and COX-2. In addition, CDD and SLC play important roles in the drug resistance of cancer cells, the effect of hypoxic conditions on CDD and SLC is unclear
