在临床恶性肿瘤的治疗中，化疗常与放疗联合使用以期获得更好的治疗效果，但药物在细胞内积累不足往往影响放化综合治疗的疗效。有机阴离子转运多肽（OATP）可辅助细胞吸收多种抗癌药物，是有效提高药物胞内累积量的关键因素。我们在所承担的上一联合基金项目的研究中发现，低剂量碳离子辐射可显著提高肿瘤细胞中OATP的表达水平，从而增强辐射后药物处理的杀伤效果，但辐射对不同类型肿瘤细胞中OATP的影响不同，可能是不同肿瘤细胞对放化综合治疗有不同响应的原因之一。本项目拟在前期工作的基础上，系统地研究不同类型肿瘤细胞受重离子辐射处理后OATP表达变化的特点，从核受体、细胞因子以及microRNA等三个方面明确OATP对重离子辐射响应的分子机制，为今后临床治疗中以OATP为靶点，有效控制肿瘤细胞辐射后的药物累积能力，提高放化联合治疗的效果提供理论依据。

The combination of chemotherapy and radiotherapy is often applied to patients during malignant tumor treatments so as to obtain better results. However, lack of accumulation of anti-tumor drugs within the cells is a problem that leads to ineffective therapeutic outcomes. Organic anion transporting polypeptides (OATPs) are membrane transporters that mediate the uptake of a wide variety of anti-tumor drugs, and hence a key determinant for cellular drug accumulation. In the previous grant funded by National Science Foundation, it was found that low dose carbon ions can significantly increase expression of OATPs within breast cancer cells, which in turn enhance the killing effect of anti-tumor drugs after irradiation. However, different kinds of tumor cells exhibited different responses toward irradiation, which possibly lead to different effectiveness of radiochemotherapy. In the proposed project, we are planning to exert systematic studies of OATPs responses within different kinds of tumor cells toward heavy ion irradiation. Further investigation of the underlying molecular mechanisms of difference responses from the aspects of nuclear receptors, cytokines and microRNAs will be carried out. The information obtained will enable us to utilize OATPs as targets to control the concentration of anti-tumor drugs after irradiation, and provide theoretical supports to increase effectiveness of radiochemotherapy.