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.
Keywords: ABCC2 , polymorphism, sensitivity, accumulation, transport