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. 2015 Sep 9;6(31):31461–31478. doi: 10.18632/oncotarget.5058

Figure 8. Metabolic basis of the chemosensitizing effects of NZ in MDR cells.

Figure 8

Self-assembling nanoparticles encapsulating zoledronic acid (NZ) inhibit the farnesyl pyrophosphate synthase (FPPS) step in the mevalonate (Mev) pathway. So doing, NZ reduces the Ras/ERK1/2/HIF-1α-mediated transcription of P-glycoprotein (Pgp), the transcription of glycolytic genes, the synthesis of ubiquinone (UQ) and the mitochondrial electron flux, thus limiting the supply of ATP for Pgp, multidrug resistance related proteins (MRPs) and breast cancer resistance protein (BCRP). Overall these events increase the intracellular retention and toxicity of chemotherapeutic drugs (d).