Kuo Wei-Ting, Tsai Yuan-Chung, Wu His-Chin, Ho Yung-Jen, Chen Yueh-Sheng, Yao Chen-Han, Yao Chun-Hsu
Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan, R.O.C.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
Oncol Rep. 2015 Nov;34(5):2351-6. doi: 10.3892/or.2015.4204. Epub 2015 Aug 19.
The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.
本研究的目的是确定山奈酚在体外和体内对肺癌是否具有放射增敏潜力。通过MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑）法、细胞周期分析和克隆形成试验，阐明了山奈酚在A-549肺癌细胞中的体外放射增敏活性。通过苏木精和伊红染色及免疫组织化学，在A-549细胞的BALB/c裸鼠异种移植模型中评估体内活性，并记录肿瘤体积。通过蛋白质印迹分析检测凋亡途径的蛋白质水平。山奈酚处理通过激活凋亡途径抑制A-549细胞的生长。然而，相同剂量对HFL1正常肺细胞生长没有影响。山奈酚诱导G2/M期细胞周期阻滞，并增强辐射诱导的死亡和克隆形成存活抑制。体内数据表明，山奈酚增加肿瘤细胞凋亡和辐射杀伤。总之，研究结果表明，山奈酚通过抑制AKT/PI3K和ERK途径以及激活线粒体凋亡途径，在体外和体内增加了辐射对肿瘤细胞的杀伤作用。本研究结果提供了确凿证据，表明山奈酚是一种安全且具有潜在放射增敏作用的药物。
