Influence of ABCB1 (1236C > T, 2677G > T and 3435C > T) polymorphisms on the transport ability of P-gp-mediated sunitinib in Caco-2 cell line

P-glycoprotein (P-gp), encoded by ABCB1 gene, participants in the transmembrane transport of multiple anticancer drugs. The aim of the current research was to observe in vitro the impacts of ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms on the efflux activity of P-gp-mediated sunitinib.Stable recombinant colonic adenocarcinoma cell (Caco-2) systems transfected with ABCB1 wild-type allele and variant alleles (1236 T, 2677T and 3435T) were constructed. The resistance of each cell line to sunitinib was assessed by cell counting kit-8 (CCK8) assay. The effects of ABCB1 (1236 C > T, 2677G > T and 3435C > T) polymorphisms on the intracellular accumulation and transepithelial permeability of sunitinib were also investigated.The recombinant cell lines transfected with ABCB1 variant alleles (1236 T, 2677T, and 3435T) showed higher resistance to sunitinib compared to cells transfecting with ABCB1 wild-type allele (p < .05). The intracellular accumulation of sunitinib was significantly decreased in the three types of recombinant cell lines overexpressing ABCB1 variant alleles in comparison of their wild-type cell lines (p < .05). The transepithelial permeability of sunitinib in recombinant cell systems in transfected with variant alleles was significantly increased compared with cells overexpressing ABCB1 wild-type allele. The P-gp activity in recombinant variant cells is stronger when mediated transport of sunitinib than wild-type counterpart. P-gp encoded by ABCB1 (1236 T, 2677T, and 3435T) variant alleles may be more efficient to transport sunitinib than wild-type allele. Our observation suggests that ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms affect the transport ability of P-gp-mediated sunitinib.Collectively, ABCB1 polymorphisms may alter the P-gp-mediated sunitinib sensitivity via regulating drug transport.