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

Objective: Multidrug resistance-associated protein 2 (MRP2), encoded by gene, is involved in the efflux of certain anticancer drugs. Here we observed whether the (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 wild-type and variant alleles were used to evaluate the sensitivity, intracellular accumulation, and transmembrane transport of paclitaxel, docetaxel, and doxorubicin.

Results: The recombinant variant cell line showed higher IC values for paclitaxel and doxorubicin than wild-type cell system (<0.01). Intracellular accumulations of paclitaxel and doxorubicin in cells transfected with variant allele were significantly decreased compared to cells transfected with wild-type allele (<0.01). The efflux ratios of paclitaxel and doxorubicin across cell line were significantly increased compared with cell system (<0.01). However, (G1249A) polymorphism had no effect on the transport activity of MRP2-mediated docetaxel.

Conclusion: Our results indicate that (G1249A) polymorphism affects the transport activities of MRP2-dependent paclitaxel and doxorubicin, resulting in greater efflux of these anticancer drugs.