Journal Article Effect of carbon ion irradiation on drug transporters organic anion transporting polypeptides

Zhou, Chao  ,  Rong, Yang  ,  Konishi, Teruaki  ,  Xiao, Yunpeng  ,  Fang, Zihui  ,  Hong, Mei

187pp.689 - 700 , 2017-04 , Radiation Research Society
Organic anion transporting polypeptides (OATPs) are a family of membrane uptake transporters that play important roles in absorption, distribution, metabolism and excretion of wide ranges of endogenous and exogenous compounds. OATP members such as OATP1A2, 1B1 and 1B3 were found to transport numerous anticancer agents. Hence, these uptake transporters have been proposed to serve as novel and potential therapeutics targets for chemotherapy. Previous studies in our laboratory demonstrated that OATP1A2 expression was up-regulated 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 on MCF7 and MDA-MB231 cells. It was found out that OATP1A2 expression was significantly up-regulated in the hormone-dependent MCF7 cells, especially when irradiated with the low dose of 0.5Gy; while for the hormone-independent MDA-MB231 cells, higher does irradiation exerted a greater effect, though only a moderate change was observed when compared with MCF7 cells. Combined treatment of OATP1A2 substrates 5-fluorouracil, paclitaxel and methotrexate with 0.5Gy irradiation resulted in greater cytotoxicity toward MCF7 cells than with the treatment of anti-neoplastic agents and higher doses. Therefore, heavy ions such as carbon ions can affect expression of drug transporter and provide a promising manner to more efficiently deliver anti-tumor drugs

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