Characterization of the Organic Anion Transporter 2 (OAT2) and its interaction with cytostatics

Abstract

The ability of a compound to exert its cytostatic effect is largely governed by transport proteins that are involved in the uptake as well as efflux of the compound from a cell. A lot of focus has been on the efflux transport systems which drive the compound out of the cell whereas relatively little is known about influx transporter systems. The knowledge about influx transporter proteins becomes all the more important in the case of tumor cells wherein, different expression patterns of influx transporters has been observed among patients. In such a scenario, administering a cytostatic to a patient with a tumor which has the expression of corresponding influx transporter supressed might lead to a drastic effect with the compound taking its toll on the surrounding tissue. We are interested in one such influx transporter, the Organic Anion Transporter 2 (SLC22A7) protein. In the current study, we performed experiments on the interaction of OAT2 stably transfected HEK cells with several cytostatics which are routinely being used in cancer chemotherapy. We found that OAT2 is strongly inhibited by the cytostatics bendamustine, irinotecan and paclitaxel. By Dixon plot analysis, we calculated the Ki values for these inhibitors to be 43.3 μM, 26.4 μM and 10.4 μM respectively. Further experiments are focused on finding out whether they are transported by OAT2 and the expression of this protein in various hepatocarcinoma cell lines.