Background:
Multidrug resistance(MDR) is a phenomenon which cells become resistance to structurally and mechanistically unrelated drugs. This is one of the major problems in cancer treatment. The over-expression of ABC transporter is one of the main causes of MDR. Among ABC transporters, P-glycoprotein(P-gp) is the most studied and well-characterized one. Therefore, developing P-gp inhibitors to overcome MDR may provide better outcomes of chemotherapy.
Aim:
The aim of the present study is to investigate whether entrapped curcumin in nanoparticle carriers could modulate P-gp function.
Method:
Recombinant P-glycoprotein-expressing HEK293 cell line was established. Real-time qRT-PCR was conducted to confirm whether curcumin-loaded nanoparticles would affect P-gp mRNA expression. Influence of curcumin-loaded nanoparticles on P-gp function was evaluated by calcein-AM uptake assay and rhodamine123 efflux assay. Inhibitory effect of curcumin-loaded nanoparticles was identified by the dose-response study of rhodamine 123 efflux.
Results:
There was no significant influence of curcumin-loaded nanoparticles on P-gp mRNA expression after 72 hr treatment. Inhibition effect of curcumin-loaded nanoparticles on P-gp function was demonstrated both in calcein-AM uptake assay and rhodamine123 efflux assay. Pretreating 1, 2.5, 5µM curcumin-loaded nanoparticles for 30, 60 minutes could significantly inhibit P-gp function. Results from rhodamine 123 efflux assay demonstrated that curcumin-loaded nanoparticles significantly inhibit P-gp efflux function with IC50 6.126µM.
Conclusion:
These results demonstrated that curcumin-loaded nanoparticles inhibited P-gp efflux function under low concentrations. This study provide new nanotherapeutic treatment strategies for MDR cancers and it will be helpful in the future in vivo studies and clinical practice.