前言: 在成人中，星狀膠質瘤是一種相當具有侵略轉移性的原位腦瘤。放射治療目前對此依舊具有顯著的治療效果，但是其中對於周邊的星狀細胞，不樂見的副作用即是正常細胞的傷害，包括細胞骨架(膠質纖維酸性蛋白)有不正常的分布且與腦損傷息息相關。
目的: 為了解決這個困境，許多的抗氧化物都曾經被用以輔助放射治療。在眾多的抗氧化物中，輔酶Q10是少數不具有使用過量幫助腫瘤生長的副作用。然而，目前已知對於輔酶Q10合併放射治療的研究是有限的。在本篇研究，我們將致力於探討輔酶Q10合併腦瘤放射治療的潛在療效。
材料與方法: 星狀細胞與星狀膠質瘤之細胞被預先培養在含有輔酶Q10的培養基中，並於其後照射伽馬射線鈷六十(60Co)達十格雷的劑量。觀察照射後造成的粒線體活性改變，膠質纖維酸性蛋白的分布情況與其他有關於細胞表現型的指標，例如:型態、爬行速度與細胞貼附面積。另外，為了模擬體內環境，我們也建立共培養的模型，分別檢視細胞存活的比例與立體入侵能力。
結果: 我們的研究結果顯示，輔酶Q10酶能夠有效維持過氧化物在癌細胞粒線體的蓄積，降低其在正常細胞的濃度，調控細胞骨架的穩定性與分布，而導致合併輻射治療有加成效果，甚至在共培養的模型中，發現即便有活化態星狀膠質細胞增強腫瘤輻射保護性，輔酶Q10也能有一樣的效果。
結論: 我們的實驗結果說明輔酶Q10對於星狀膠質細胞的保護性，並且在共培養模型中發現輔酶Q10能增加放射治療的成效，此外，輔酶Q10能維持星狀細胞的正常功能與降低癌細胞的惡性程度，因此，輔酶Q10能改善暴露劑量產生的負面影響並使星狀膠質細胞損傷程度降低進而提升放射治療的療效。

Introduction: Astrocytoma is an aggressive primary malignant brain tumor in adults. Radiation therapy has been an effective medical treatment, but one of its undesired side-effects is the induced cell damage of surrounding astrocytes, which can lead abnormal distribution of Glial fibrillary acidic protein and associates with severe brain injury [1].
Purpose: In order to cope with this problem, various antioxidants have been applied with radiation therapy. Among antioxidants, the Coenzyme Q10 (Q10) is one of the few candidates without tumor promotional effect. However, the understanding about Q10 therapeutic effect on radiological protection is limited. In this study, we aimed to investigate the potential therapeutic effects of Q10 on brain tumor radiation treatment.
Materials and Methods: Astrocyte and glioma cell lines were cultivated with Q10 and treated with to 10Gy single dose of Cobalt-60 (60Co) γ-ray. Mitochondrial viability was analyzed using MTT assay, GFAP responses was analyzed by immunofluorescence staining and quantitative reverse transcription polymerase chain reaction, and other cell phenotype indices, such as the morphology and migration. Moreover, to simulate the microenvironment within the human body, we further evaluated tumor invasion ability and cell viability in co-culture model.
Results: Our results indicated that radiation with Q10 treatment triggered high concentration of mitochondrial ROS in astrocytoma, but not in astrocyte. In addition, Q10 reduce the GFAP interference by radiation, by which indicated minor injury of astrocyte and reducing astrocytoma migration. From the 2D and 3D co-culture models, combined with radiation treatment, we showed Q10 can eliminate the tumor progression.
Conclusions: Our results demonstrated that Q10 can improve the therapeutic effectiveness of radiation therapy in vitro. With further studies, we expected Q10 can benefit glioma treatment in near future.

中文摘要 i
Abstract ii
Table of Contents iv
List of Figures vii
Chapter1. Introduction 1
1.1 Radiation therapy on brain tumor 1
1.2 Therapeutic effect of Coenzyme Q10 on various cancer researches 3
1.3 Importance of Glial fibrillary acidic protein (GFAP) 5
1.4 Research purpose and structure 7
Chapter2. Materials and Methods 9
2.1 Experimental Material 9
2.2 Cell Lines and Subculture 9
2.2.1 Cell lines 9
2.2.2 Subculture 9
2.3 Experimental Protocol 10
2.3.1 Reagent preparation 10
2.3.2 Radiation treatment 10
2.3.3 Real-time qPCR analysis 11
2.3.4 Immunofluorescence staining 11
2.3.5 Fluorescence microscopy 12
2.3.6 96-well plate fabrication and 3D Spheroid formation 12
2.3.7 3D invasion assay 12
2.3.8 MTT assay 13
2.3.9 mROS production assay 13
2.3.10 Intracellular ROS staining and Viability assay for Flow Cytometry 14
2.3.11 Wound healing assay 14
2.3.12 Statistical analysis 14
Chapter3. Results and Discussion 16
3.1 Influence of Q10 on radio-resistance in 2D co-culture model 16
3.1.1 2D co-culture model establish 16
3.1.2 Determine the labeling concentration and confirm the labeling efficiency 19
3.1.3 Cell viability assay in 2D co-culture model 23
3.2 Influence of Q10 on radio-resistance in 3D co-culture model 26
3.2.1 Tumor spheroid formation with surface modification 26
3.2.2 3D Invasion assay measurement 29
3.3 Compounding effect of radiation and Q10 treatment in astrocyte 31
3.3.1 Normal astrocyte remains high radiation resistance in early stage 31
3.3.2 Q10 regulates oxidative stress balance of normal astrocyte after radiation exposure 32
3.3.3 Q10 modulates GFAP network of astrocyte after radiation treatment 35
3.3.4 Q10 alters injury response of astrocyte cell area and migration speed 38
3.4 Compounding effect of radiation and Q10 treatment in astrocytoma 40
3.4.1 Radio-sensitizing effect of Q10 on astrocytoma cell in early stage 40
3.4.2 Q10 maintains mitochondrial oxidative stress in astrocytoma after radiation treatment 42
3.4.3 Q10 eliminates the cell stress of astrocytoma via GFAP network 44
3.4.4 Q10 eliminates the deterioration possibility and metastatic ability of astrocytoma radiation treatment- cell area and migration speed 46
Chapter4. Conclusion and Future works 51
References 54

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