Background: Use of ionizing radiation (IR) is a common therapeutic modality for patients with colon carcinoma, although resistance of cancer cells and unintended toxicity reduce clinical outcomes.

Purpose: To enhance radioresponse of colon cancer cells, we designed a novel approach using auraptene (AUR) in combination with ionizing radiation (IR).

Methods: For in vitro studies, CT26 cells were pretreated with AUR and irradiated at different doses. Then, cell viability was evaluated by alamarBlue assay, and the mechanism of cell death was elucidated using annexin V-PI. To determine efficacy of our combined therapeutic modality in vivo, AUR was injected intraperitoneally to murine models of colon carcinoma followed by IR, and then quantitative measurements and histopathological examinations were performed. For molecular analyses, real time PCR and Western blot were carried out.

Results: Assessment of cell viability indicated significant enhancement of IR effects by AUR that was also confirmed by increased number of apoptotic cells. In vivo studies further demonstrated improved outcome in IR, since significant regression in tumor size was observed after administration of AUR + IR. Molecular analyses revealed down regulation of Cyclin D1 and CD44, along with involvement of PI3K-AKT-mTORC signaling pathway and Caspase-3 in observed combinatorial effects.

Conclusion: Taken together, current findings support our previous reports on sensitizing effects of AUR and that AUR could be used as a promising adjunct to IR in cancer treatment.

背景：尽管癌细胞的耐药性和意外毒性降低了临床结果，但电离辐射（IR）是结肠癌患者的一种常见治疗方式。

目的：为了增强结肠癌细胞的放射反应，我们设计了一种新的方法，将紫杉醇（AUR）与电离辐射（IR）结合使用。

方法：为了进行体外研究，将CT26细胞用AUR预处理并以不同剂量照射。然后，通过alamarBlue测定法评估细胞活力，并使用膜联蛋白V-PI阐明细胞死亡的机制。为了确定我们联合治疗方法在体内的功效，将AUR腹膜内注射到结肠癌的小鼠模型中，然后进行IR，然后进行定量测量和组织病理学检查。对于分子分析，进行实时PCR和蛋白质印迹。

结果：对细胞活力的评估表明AUR对IR的作用明显增强，凋亡细胞数量的增加也证实了这一点。体内研究进一步证实了IR的改善，因为在给予AUR + IR后观察到肿瘤大小显着消退。分子分析显示，Cyclin D1和CD44的下调，以及PI3K-AKT-mTORC信号通路和Caspase-3参与所观察到的组合效应。

结论：综上所述，目前的发现支持了我们先前关于AUR致敏作用的报道，并且AUR可以用作癌症治疗中IR的有希望的辅助手段。