Effect of Carbon-Ion Radiation on Drug Transporters Organic Anion Transporting Polypeptides in Breast Cancer Cells.

Abstract

Organic anion transporting polypeptides (OATPs) are a family of membrane uptake transporters that play important roles in absorption, distribution, metabolism and excretion of a wide range of endogenous and exogenous compounds. OATP members, such as OATP1A2, 1B1 and 1B3, were found to transport numerous anticancer agents. For this reason, these uptake transporters have been proposed to serve as novel and potential therapeutic targets for chemotherapy. Previously published studies from our laboratory demonstrated that OATP1A2 expression was upregulated in breast cancer MCF7 cells after X-ray irradiation and the transport of its substrate methotrexate was increased. In the current study, we investigated the effect of carbon-ion radiation on MCF7 and MDA-MB231 cells. We observed significant upregulation of OATP1A2 expression in the hormone-dependent MCF7 cells, especially when irradiated with a low dose (0.5 Gy). For the hormone-independent MDA-MB231 cells, while irradiation with a higher dose exerted a greater effect, only a moderate change was observed compared to that of the MCF7 cells. Combined treatments of OATP1A2 substrates 5-fluorouracil, paclitaxel and methotrexate with 0.5 Gy irradiation resulted in greater cytotoxicity toward MCF7 cells than with the treatment of antineoplastic agents and higher doses. Therefore, heavy ions, such as carbon, can affect expression of drug transporters and show promise in facilitating the delivery of antitumor drugs with greater efficiency.