Naumann Patrick, Liermann Jakob, Fortunato Franco, Schmid Thomas E, Weber Klaus-Josef, Debus Jürgen, Combs Stephanie E
Department of Radiation Oncology, University Clinic Heidelberg, Heidelberg, Germany.
Department of General, Visceral and Transplantation Surgery, University Clinic Heidelberg, Heidelberg, Germany.
PLoS One. 2017 Jul 10;12(7):e0180940. doi: 10.1371/journal.pone.0180940. eCollection 2017.
Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT).
In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT.
Both SFN and RT show a strong and dose dependent survival reduction in clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in γH2AX protein level indicating DNA damage. Effects were more pronounced in combined treatment and both cell cycle perturbation and DNA damage persisted for a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA repair proteins Ku 70, Ku 80 and XRCC4.
Our results suggest that combination of SFN and RT exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer.
萝卜硫素（SFN）是一种富含于西兰花和菜花等十字花科蔬菜中的草本异硫氰酸盐，因其对胰腺癌等细胞系具有抗肿瘤作用而受到关注。有报道称其对头颈部癌具有抗增殖和放射增敏特性，但关于其与放疗（RT）联合应用对胰腺癌细胞的影响却知之甚少。
在四种已建立的胰腺癌细胞系中，我们研究了克隆形成存活率，分析了细胞周期分布，并通过流式细胞术和蛋白质免疫印迹法比较了用SFN和RT处理后的DNA损伤情况。
在克隆形成试验中，SFN和RT均显示出强烈的剂量依赖性存活降低，诱导G2/M期细胞周期阻滞，并增加γH2AX蛋白水平，表明存在DNA损伤。联合治疗的效果更明显，细胞周期紊乱和DNA损伤持续的时间比单独使用SFN或RT后更长。此外，SFN导致DNA修复蛋白Ku 70、Ku 80和XRCC4缺失。
我们的结果表明，与单独的每种治疗相比，SFN和RT联合应用对DNA的损伤和生长抑制作用更显著。SFN似乎是提高胰腺癌新辅助治疗后化疗放疗疗效以及有望提高二次切除率的可行选择。
