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Published on: May 27, 2016
In vitro Transport Ability of ABCC2 (G1249A) Polymorphic Variant Towards Anticancer Drugs
Guo Lian1, Jia Yuan2, Yuan Gao1
1Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441021, People's Republic of China.
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 IC50 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.
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