In vitro Transport Ability of ABCC2 (G1249A) Polymorphic Variant Towards Anticancer Drugs

OBJECTIVE: Multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2 gene, is involved in the efflux of certain anticancer drugs. Here we observed whether the ABCC2 (G1249A) polymorphism impacts the transport abilities of MRP2-dependent paclitaxel, docetaxel, and doxorubicin in recombinant LLC-PK1 cell lines. METHODS: LLC-PK1 cell lines transfected with ABCC2(1249G) wild-type and ABCC2(1249A) variant alleles were used to evaluate the sensitivity, intracellular accumulation, and transmembrane transport of paclitaxel, docetaxel, and doxorubicin. RESULTS: The recombinant ABCC2(1249A) variant cell line showed higher IC(50) values for paclitaxel and doxorubicin than ABCC2(1249G) wild-type cell system (p<0.01). Intracellular accumulations of paclitaxel and doxorubicin in cells transfected with ABCC2(1249A) variant allele were significantly decreased compared to cells transfected with ABCC2(1249G) wild-type allele (p<0.01). The efflux ratios of paclitaxel and doxorubicin across ABCC2(1249A) cell line were significantly increased compared with ABCC2(1249G) cell system (p<0.01). However, ABCC2 (G1249A) polymorphism had no effect on the transport activity of MRP2-mediated docetaxel. CONCLUSION: Our results indicate that ABCC2 (G1249A) polymorphism affects the transport activities of MRP2-dependent paclitaxel and doxorubicin, resulting in greater efflux of these anticancer drugs.