Effect of Carbon-Ion Radiation on Drug Transporters Organic Anion Transporting Polypeptides in Breast Cancer Cells
Effect of Carbon-Ion Radiation on Drug Transporters Organic Anion Transporting Polypeptides in Breast Cancer Cells
复制标题
碳离子辐射对乳腺癌细胞中药物转运蛋白有机阴离子转运多肽的影响
DOI：
10.1667/rr14603.1
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发表时间：
2017-06-01
影响因子：
3.4
通讯作者：
Hong, Mei
中科院分区：
文献类型：
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作者：
Zhou, Chao;Rong, Yang;Hong, Mei
有机阴离子转运多肽（organic anion transporting polypeptides，OATPs）是一类膜摄取转运蛋白家族，在多种内源性和外源性物质的吸收、分布、代谢和排泄中发挥重要作用。OATP成员，如OATP 1A 2、1B 1和1B 3，被发现转运多种抗癌药物。由于这个原因，这些摄取转运蛋白已被提出作为新的和潜在的化疗治疗靶点。我们实验室先前发表的研究表明，X射线照射后乳腺癌MCF 7细胞中OATP 1A 2表达上调，其底物甲氨蝶呤的转运增加。在本研究中，我们研究了碳离子辐射对MCF 7和MDA-MB 231细胞的影响。我们观察到OATP 1A 2表达的显着上调，在乳腺癌依赖性MCF 7细胞，特别是当用低剂量（0.5戈伊）照射。对于不依赖于细胞毒性的MDA-MB 231细胞，虽然用更高剂量照射产生更大的效果，但与MCF 7细胞相比仅观察到中等变化。OATP 1A 2底物5-氟尿嘧啶、紫杉醇和甲氨蝶呤与0.5戈伊照射的联合治疗导致对MCF 7细胞的细胞毒性大于使用抗肿瘤剂和更高剂量的治疗。因此，重离子，如碳，可以影响药物转运蛋白的表达，并显示出促进更高效率的抗肿瘤药物的递送的前景。
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.