OncoTargets and Therapy (Feb 2020)
In vitro Transport Ability of ABCC2 (G1249A) Polymorphic Variant Towards Anticancer Drugs
Abstract
Guo Lian, 1 Jia Yuan, 2 Yuan Gao 1 1Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441021, People’s Republic of China; 2Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Ats and Science, Xiangyang, Hubei 441021, People’s Republic of ChinaCorrespondence: Yuan GaoDepartment of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 136 Jingzhou Road, Xiangyang, People’s Republic of ChinaTel +86 18327506946Email [email protected]: 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
