Effect of OATP1B1 genetic polymorphism on the uptake of tamoxifen and its metabolite, endoxifen.

ABSTRACT

Overexpression lentivirus platform was established of OATP1B1 (organic anion transporting polypeptides 1B1) wild­type and mutant type genetic polymorphism in vitro, and using this platform we investigated and compared the uptake of tamoxifen and its metabolites by mutating the 388 and the 521 bases. The overexpression lentivirus cell platforms were successfully constructed, including OATP1B1*1a-HEK293T and OATP1B1*1b-HEK293T and OATP1B1*5-HEK293T cell model, the infection efficiency is not less than 80%. It shows a high level of gene expression at the mRNA and protein level. The tamoxifen and endoxifen can be taken up into the cells through organic anion transporter polypeptide 1B1, and OATP1B1521T>C inhibits the function of the transport protein, resulting in the content of drug in cell lysis liquid in OATP1B1*5-HEK293T group is lower than in OATP1B1*1a-HEK293T group (tamoxifen or endoxifen), with statistical significance. The content of the drug in cell lysis liquid in OATP1B1*1b-HEK293T group and the OATP1B1*1a-HEK293T group, similar with no statistical significance. These results suggest that tamoxifen and endoxifen can be transported by OATP1B1. However, OATP1B1 521T>C can inhibit the effects of OATP1B1 on tamoxifen and endoxifen in the cells.