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Targeted chemotherapy for hepatocellular carcinoma (HCC) is impaired by intrinsic and/or acquired drug resistance. Since drugs used in HCC therapy (e.g. anthracyclines or the tyrosine kinase inhibitor sorafenib) are substrates of uptake and/or efflux transporters, variable expression of these transporters at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. In this study, the variability of expression of uptake (OCT1, OCT3) and efflux transporters (MDR1/P-glycoprotein, MRP1, MRP2, BCRP), selected for their implication in transporting drugs used in HCC therapy, was investigated. HCC and corresponding non-tumor tissue samples were collected from 24 Japanese patients at time of surgery. Protein expression was determined by immunohistochemistry. Expression data were correlated with clinicopathological characteristics and patients’ outcome (median follow-up 53 months). Generally, expression was highly variable among individual tumor samples. Yet, median expression of OCT1, OCT3 and MDR1 in HCC was significantly lower (1.4-, 2.7and 2-fold, respectively) than in non-tumor tissue, while expression of MRP2 persisted and BCRP showed a trend of increased levels in HCC. Patients with low BCRP expression had a significantly shorter overall and recurrencefree survival time. Results suggest different expression patterns of drug transporters in HCC, which are only in part associated with clinicopathological characteristics. Detailed information of expression of drug transporters in HCC may be promising for individualization and optimization of drug therapy of liver cancer. This article has not been copyedited and formatted. The final version may differ from this version. DMD Fast Forward. Published on September 17, 2014 as DOI: 10.1124/dmd.114.059832 at A PE T Jornals on M ay 1, 2017 dm d.aspurnals.org D ow nladed from