肿瘤细胞的辐射抵抗是导致放疗失败的主要原因，而DNA损伤修复与肿瘤细胞代谢的改变则是决定肿瘤放疗抵抗的重要因素。我们近期研究发现，从泰山白首乌中分离得到的C21甾体化合物-告达庭能够诱导乳腺癌细胞DNA发生断裂，并且上调DNA损伤标志分子γ-H2AX的表达。同时，告达庭能够抑制细胞内乳酸生成和己糖激酶 (HK-2) 的表达。本项目拟在证实告达庭对乳腺癌具有放疗增敏作用的基础上，从抑制DNA损伤修复和调节肿瘤细胞糖酵解途径等方面阐明告达庭降低乳腺癌放疗抵抗的分子机理。综合运用免疫印迹、免疫荧光与辐射细胞生物学效应检测等研究手段，阐明告达庭调控肿瘤细胞DNA损伤应答和糖类代谢与其增加乳腺癌放射敏感性的内在联系。项目的实施在丰富告达庭抑癌活性分子机理的同时，为中药资源开发利用及乳腺癌临床治疗提供新思路和理论指导。

Radioresistance is the main cause of radiotherapy failure. DNA damage repair and the change of tumor metabolism are primary factors leading to radioresistance. Our recently studies showed that caudatin, a C21 steroidal aglycone isolated from Cynanchum bungei, could induce DNA damage and increase the expression of γ-H2AX, a marker of DNA damage. Moreover, caudatin treatment inhibited the production of lactate and downregulated the expression of HK-2 in breast cancer cells. Based on the findings of caudatin increasing the radiosensitivity of breast cancer, we mainly investigate the molecular mechanisms that caudatin sensitizes breast cancer cells to radiation therapy by inhibiting the DNA damage repair and aerobic glycolysis in this project. We take combinatory approaches of a variety of experimental techniques, such as western blotting, immunofluorescence technique and assays of biological response to ionizing radiation to explore the molecular mechanisms that caudatin enhances radiosensitivity through regulating DNA damage response and aerobic glycolysis in human breast cancer cells. Implementation of the project will illustrate the anti-tumor mechanisms for caudatin, and provide theoretical base for exploiting the resource of traditional Chinese herbal medicine and human breast cancer therapy.