GQDs Reverse Multidrug Resistance Genes And Its Mechanism

Multidrug resistance(MDR)is one of the most important drug-resistant forms of cancer cells,glycoprotein-mediated resistance mechanisms of tumor cells is a very common cause.In recent years,researcher have been found associated with MDR transmembrane transporter protein.Over-expression of P-glycoprotein(P-gp),Multidrug resistance protein 1(MRP1),Breast cancer resistance protein(BCRP)are associated with the development of MDR.They are members of the ABC(ATP-bindingcassette transporter)superfamily.P-gp uses ATP to transport a wide variety of structurally unrelated cytotoxic compounds out of the cell,resulting in lowering effect of chemotherapy.Previous work in our laboratory found that graphene quantum dots could increase the accumulation of doxorubicin in MCF-7 cells,reversing drug resistance in MCF-7 cells and inhibit efflux doxorubicin,thus could be used to improve the effect of chemotherapy.On the basis of this result,we try to further explore the mechanism of graphene quantum dots reversing MDR in drug resistant tumor cells cell,using cytotoxicity assay,cell fluorescence,Western Blot and RT-PCR experiments.We found that GQDs efficiently facilitate the cellular uptake of doxorubicin(DOX)in HL60/ADR and A549/DDP cells.Cytotoxicity of DOX was also significantly increased by pre-incubation with GQDs with the cells.However,in the Hela,A549,7721 cells,no effect was observed under the same experimental condition,which suggests that incubation with GQDs possibly is associated with Multi drug resistance associated protein 1(MRP1)that is responsible for the efflux of the drug molecules.We focused on GQDs and MRP1 transporters to further explore the possible mechanisms of GQDs' inhibition of multidrug resistance.GQDs treatment resulted in the decrease of protein expression level and RNA transcript level of MRP1,On the basis of our previous finding that GQDs could stabilize and induce the formation of i-motif structure,we propose that GQDs decreased the RNA transcript level of MRP1 by inducing the formation of i-motif structure in C-rich promoter region of MRP1 gene.These findings suggest that GQDs could be possibly used to reverse the MDR of the cells,holding a great potential in cancer therapy.