Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Shonai Regional Industry Promotion Center, Tsuruoka, Japan.
Anticancer Res. 2021 Dec;41(12):6023-6029. doi: 10.21873/anticanres.15421.
BACKGROUND/AIM: Carbon-ion radiotherapy has strong antitumor effects in X-ray-resistant tumors. However, the mechanisms underlying the strong antitumor effect, especially on metabolic alterations, are not fully elucidated. This study aimed to determine the effect of therapeutic carbon ions on metabolic alterations in cancer cells.
Five human cancer cell lines were used in this study. The change in 333 metabolite levels in response to carbon ions was analyzed using gas chromatography-mass spectrometry.
Fifty-two metabolites were commonly detected in all cell lines. The levels of five metabolites significantly changed in four or more cell lines. Three of the five metabolites (i.e., 2-ketoglutaric acid, fumaric acid and 2-hydroxyglutaric acid) were associated with the TCA cycle. TCA cycle intermediates and the downstream oncometabolite 2-hydroxyglutaric acid were up-regulated by carbon ions.
We demonstrated for the first time that TCA cycle intermediates and 2-hydroxyglutaric acid are up-regulated after carbon-ion irradiation.
背景/目的：碳离子放疗对 X 射线抵抗性肿瘤具有强大的抗肿瘤作用。然而，其强大抗肿瘤作用的机制，特别是代谢改变的机制，尚未完全阐明。本研究旨在确定治疗性碳离子对癌细胞代谢改变的影响。
本研究使用了 5 个人类癌细胞系。使用气相色谱-质谱联用分析了碳离子作用下 333 种代谢物水平的变化。
在所有细胞系中均共同检测到 52 种代谢物。在 4 种或更多细胞系中，有 5 种代谢物的水平显著变化。这 5 种代谢物中的 3 种（即 2-酮戊二酸、富马酸和 2-羟基戊二酸）与 TCA 循环有关。TCA 循环中间产物和下游致癌代谢物 2-羟基戊二酸均被碳离子上调。
我们首次证明，碳离子照射后 TCA 循环中间产物和 2-羟基戊二酸上调。
