Background

Since its discovery in the late 19^th century, radiotherapy has been one of the most important medical treatments in oncology. Recently, fasting or short-term starvation (STS) in cancer patients undergoing chemotherapy has been studied to determine its potential for enhancing the therapeutic index and for preventing side- effects, but no data are available in the radiotherapy setting. We thus decided to investigate the effects in vitro of STS in combination with radiotherapy in metastatic cancer cells and non-cancer cells.

Methods

Cells were incubated in short-term starvation medium (STS medium, 0·5 g/L glucose + 1% FBS) or in control medium (CM medium, 1 g/L glucose + 10 % FBS) for 24 h and then treated with single high-dose radiation. A plexiglass custom-built phantom was used to irradiate cells. DNA damage was evaluated using alkaline comet assay and theCometAnalyser software. The cell surviving fraction was assessed by clonogenic assay.

Finding

STS followed by single high-dose radiation significantly increased DNA damage in metastatic cancer cell lines but not in normal cells. Furthermore, STS reduced the surviving fraction of irradiated tumor cells, indicating a good radio-sensitizing effect on metastatic cell lines. This effect was not observed in non-tumor cells.

Interpretation

Our results suggest that STS may alter cellular processes, enhancing the efficacy of radiotherapy in metastatic cancer cellsin vitro. Interestingly, STS has radioprotective effect on the survival of healthy cells.

中文翻译：

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放疗和短期饥饿联合对转移性和非肿瘤细胞系的影响。

背景

自从已故发现19^个世纪，放射治疗一直是肿瘤学中最重要的医学治疗之一。最近，已对正在接受化疗的癌症患者的禁食或短期饥饿（STS）进行了研究，以确定其增强治疗指数和预防副作用的潜力，但是在放射治疗中尚无数据。因此，我们决定研究STS联合放射疗法在转移性癌细胞和非癌细胞中的体外作用。

方法

将细胞在短期饥饿培养基（STS培养基，0·5 g / L葡萄糖+ 1％FBS）或对照培养基（CM培养基，1 g / L葡萄糖+ 10％FBS）中孵育24小时，然后用单次大剂量放射。使用有机玻璃定制的体模照射细胞。使用碱性彗星试验和CometAnalyser软件评估DNA损伤。通过克隆形成测定评估细胞存活分数。

寻找

STS继之以高剂量单次辐射显着增加了转移癌细胞系中的DNA损伤，而正常细胞中则没有。此外，STS减少了放射肿瘤细胞的存活率，表明对转移细胞系具有良好的放射增敏作用。在非肿瘤细胞中未观察到这种作用。

解释

我们的结果表明，STS可能会改变细胞过程，从而增强放射治疗在体外转移癌细胞中的功效。有趣的是，STS对健康细胞的存活具有放射防护作用。