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One of the main functions of liver is the systemic elimination of many exogenous and endogenous substances. In order to perform this function, the initial step is their uptake from blood into the hepatocytes by specific transporter proteins. Many of such proteins constitute the solute carrier (SLC) superfamily. Our work deals with two proteins belonging to the SLC superfamily, the organic anion transporting polypeptides 1B1 and 1B3 which are highly expressed on the basolateral membranes of hepatocytes. We studied these two proteins in stably transfected human embryonic kidney cells using estrone sulfate and cholecystokinin octapeptide 8 (CCK8) as substrates for OATP1B1 and OATP1B3 respectively. Cis‐inhibition experiments were performed to evaluate the interactions of these proteins with cytostatics. Our experiments showed that OATP1B1 interacts strongly with vinblastine and paclitaxel. Ki values of OATP1B1 for vinblastine and paclitaxel were calculated to be 16.87 µM and 0.85 µM respectively. On the other hand, OATP1B3 dependent CCK8 uptake was inhibited in the presence of a variety of cytostatics viz., chlorambucil, bendamustine, doxorubicin, mitoxantrone, vincristine, vinblastine, paclitaxel and etoposide. From our experiments it is clear that these transporters play a crucial role in the uptake of cytostatics into hepatocytes and hence in systemic elimination of these drugs from the body. Grant Funding Source: Deutsche Forschungsgemeinschaft GRK 1034

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.