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放疗和短期饥饿联合作用对转移细胞系和非肿瘤细胞系的影响。

Effects of radiotherapy and short-term starvation combination on metastatic and non-tumor cell lines.

机构信息

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy.

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy.

出版信息

DNA Repair (Amst). 2020 Nov;95:102949. doi: 10.1016/j.dnarep.2020.102949. Epub 2020 Aug 16.

Abstract

BACKGROUND

Since its discovery in the late 19 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.

摘要

背景

自 19 世纪发现以来,放射疗法一直是肿瘤学中最重要的医学治疗方法之一。最近,对接受化疗的癌症患者进行禁食或短期饥饿(STS)治疗以确定其增强治疗指数和预防副作用的潜力进行了研究,但在放射治疗环境中尚无数据。因此,我们决定研究 STS 联合放射治疗对转移性癌细胞和非癌细胞的体外影响。

方法

将细胞在短期饥饿培养基(STS 培养基,0.5g/L 葡萄糖+1% FBS)或对照培养基(CM 培养基,1g/L 葡萄糖+10% FBS)中孵育 24 小时,然后用单高剂量辐射处理。使用定制的有机玻璃体模对细胞进行照射。使用碱性彗星试验和 CometAnalyser 软件评估 DNA 损伤。通过集落形成试验评估细胞存活分数。

结果

STS 后进行单次高剂量辐射显着增加了转移性癌细胞系的 DNA 损伤,但对正常细胞没有影响。此外,STS 降低了受照射肿瘤细胞的存活分数,表明对转移性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,增强转移性癌细胞系的放射治疗效果。有趣的是,STS 对健康细胞的存活具有放射保护作用。

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