Abstract

BackgroundRadiotherapy 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.MethodsCells 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. 1H NMR spectroscopy was employed to determine the Lac/Cr ratio.ResultsThe DNA damage increased in a radiation dose-dependent manner (p < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-ι level decreased (C6, p < 0.01; U251, p < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level.ConclusionThe 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.

Highlights

  • Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor

  • To establish whether the Lac/Cr ratio can be used as a noninvasive monitor for radiotherapy, we evaluated the correlation between this ratio, the protein kinase C (PKC)-ι expression level and apoptosis in glioma cells

  • To further our ability to noninvasively evaluate the effects of radiotherapy, we focused here on confirming that the Lac/Cr ratio correlated with apoptosis in glioma cells and that the 1H Proton nuclear magnetic resonance (NMR) spectroscopy is a viable means to monitor the Lac/Cr ratio

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Summary

Introduction

Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is 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. We evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. Li et al Cellular & Molecular Biology Letters (2018) 23:27 studies demonstrated that DNA damage could induce tumor cell apoptosis, and that this is associated with protein kinase C (PKC) activation [3,4,5,6,7]. We recently demonstrated that X-ray irradiation could lead to inhibition of PKC-ι activity, and that this correlated with the radiosensitivity of the cells [9]

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