与低LET射线相比，高LET电离辐射具有相对生物学效应高、氧增比低、能量更准确集中地传送到特定靶点等特点，在肿瘤治疗中具有较大的潜力，因此近年来国内外都开展了相关的研究与应用。在临床的恶性肿瘤治疗中，化疗常与放疗联合使用以期获得更好的治疗效果，然而，药物在细胞内积累不足往往影响放化综合治疗的疗效。药物转运蛋白是影响细胞内药物积累的关键因素，已有研究发现X射线的辐射会造成外排转运蛋白表达增加，造成肿瘤细胞的耐药性。正在进入临床应用的重离子辐射会否对外排转运蛋白具有类似影响、是否也会导致辅助细胞吸收药物的转运蛋白发生变化等问题，尚未见报道。本项目拟以重离子辐射对转运蛋白的影响为介入点，以外排转运蛋白P-糖蛋白和乳腺癌耐药蛋白以及吸收转运蛋白OATP家族成员为对象，研究高LET碳离子辐射对肿瘤细胞中转运蛋白的影响，了解其作用特点及机制，探讨转运蛋白作为目标靶点，提高综合治疗中药物吸收的效果。

High LET ionizing radiation has advantages such as high relative biological effectiveness (RBE), low oxygen enhancement ratio (OER) as well as more precisely and intensely targeted to the tumor cells compared to the traditional low LET ionizing radiation like X-ray and γ-ray, and thus seems to be a novel manner of radiation therapy with high potential. Chemotherapy and radiotherapy are often combined in clinical treatment of malignant tumors. However, failure to accumulate sufficient concentrations of anti-tumor drugs within tumor cells often affects the efficiency of the combined therapy. Drug transporters on cell membrane are key determinants for drug accumulations. It has been reported that the exprssion of efflux drug transporters such as P-glycoprotein was elevated after X-ray irradiation, and thus may lead to multi-drug resistance of the cancer cells. Whether high LET irradiation can cause similar effects and besides efflux transporters, whether uptake transporters are also affected by radiation remain unclear. In the proposed project, we are going to use breast cancer cell lines MCF-7 and MDA-MB-231 as study models to assess the effect of high LET carbon ions on the expression of efflux transporters P-glycoprotein and breast cancer resistant proteins as well as uptake transporters OATP1A2, OATP1B1 and OATP1B3. Moreover, we will also explore the underlying mechanism(s) of such an effect and investigate whether drug transporters can be utilized as a target for anti-neoplastic drug delivery in the process of combined radio- and chemotherapy.