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通过 H NMR 光谱测量乳酸与肌酸的比值,可用于非侵入性地评估 X 射线照射后神经胶质瘤细胞的细胞凋亡。

Measuring the lactate-to-creatine ratio via H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation.

机构信息

1Department of Radiology, the Second Hospital of Shandong University, Jinan, China.

2Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012 China.

出版信息

Cell Mol Biol Lett. 2018 Jun 15;23:27. doi: 10.1186/s11658-018-0092-2. eCollection 2018.

Abstract

BACKGROUND

Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells.

METHODS

Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. H NMR spectroscopy was employed to determine the Lac/Cr ratio.

RESULTS

The DNA damage increased in a radiation dose-dependent manner ( < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6,  < 0.01; U251,  < 0.05), and the p-PKC-ι level decreased (C6,  < 0.01; U251,  < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level.

CONCLUSION

The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.

摘要

背景

放射治疗是治疗神经胶质瘤(最常见的原发性脑肿瘤之一)的常用方法之一。为了无创评估放射治疗的效果,肿瘤学家必须监测 X 射线照射对神经胶质瘤细胞的影响。初步研究表明,蛋白激酶 C 亚型 ι(PKC-ι)的表达与 X 射线照射诱导的肿瘤细胞凋亡相关。乳酸/肌酸(Lac/Cr)比值也可作为评估 X 射线照射后神经胶质瘤细胞凋亡的生物标志物。本研究旨在评估神经胶质瘤细胞中 Lac/Cr 比值、凋亡率和蛋白激酶 C 亚型 ι(PKC-ι)表达之间的关系。

方法

将神经胶质瘤细胞系 C6 和 U251 的细胞随机分为 4 组,分别用 0、1、5、10 和 15 Gy 的 X 射线照射。采用单细胞凝胶电泳(SCGE)评估 DNA 损伤。流式细胞术检测细胞周期阻滞和凋亡率。Western blot 分析检测磷酸化蛋白激酶 C 亚型 ι(p-PKC-ι)水平。采用 H NMR 波谱法测定 Lac/Cr 比值。

结果

DNA 损伤随辐射剂量增加呈剂量依赖性增加(<0.05)。随着 X 射线照射的增加,凋亡率也增加(C6,<0.01;U251,<0.05),p-PKC-ι 水平降低(C6,<0.01;U251,<0.05)。p-PKC-ι 水平与凋亡呈负相关,而 Lac/Cr 比值与 p-PKC-ι 水平呈正相关。

结论

Lac/Cr 比值随 X 射线照射增加而降低,可作为反映 X 射线照射对神经胶质瘤细胞影响的生物标志物。

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