Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2

摘要: Abstract Sunitinib is an ATP-competitive multi-targeted tyrosine kinase inhibitor. In this study, we evaluated the possible interaction of sunitinib with P-glycoprotein (P-gp, ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), breast cancer (BCRP, ABCG2) and lung-resistance (LRP) in vitro . Our results showed that completely reverse drug mediated by ABCG2 at a non-toxic concentration 2.5 μM has no significant reversal effect on ABCB1-, ABCC1- LRP-mediated resistance, although small synergetic was observed combining conventional chemotherapeutic agents ABCB1 overexpressing MCF-7/adr parental sensitive MCF-7 cells, ABCC1 C-A120 KB-3-1 cells. significantly increased intracellular accumulation rhodamine 123 doxorubicin remarkably inhibited efflux methotrexate ABCG2-overexpressing also profoundly transport [ 3 H]-methotrexate ABCG2. However, did not affect expression mRNA or levels. addition, block phosphorylation Akt Erk1/2 Overall, conclude reverses ABCG2-mediated MDR through inhibiting function These findings may be useful for combinational therapy clinic.