博碩士論文 106827005 詳細資訊




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姓名 高銘澤(Ming-Tse Kao)  查詢紙本館藏   畢業系所 生物醫學工程研究所
論文名稱 靜磁場於癌細胞的生物效應
(The static magnetic field-mediated biological effects on cancer cells)
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摘要(中) 許多文獻指出,細胞生理會受到電場和磁場的電磁力影響。另外,細胞會受磁場不同的
物理參數而影響癌細胞的生長,如磁場頻率、梯度和強度等。靜磁場常被用於研究特定
磁場強度下的生物效應,然而靜磁場影響細胞的生理機制仍懸而待解且存在爭議。因此,
本研究要探討靜磁場如何調控癌細胞生理機制。在本研究中,細胞實驗結果顯示靜磁場
會調控癌細胞的生長速率及細胞週期。根據細胞生長速率的實驗結果指出,受磁組細胞
的數量增加一倍所需時間比對照組長。此外,細胞週期的實驗結果顯示在靜磁場(static
magnetic field,SMF)下暴露 24 小時後,與對照組相比受磁組有更多累積於分裂期的
比例(% of G2/M,SMF:控制組= 5.50 : 0.25)。在免疫螢光染色及西方點墨法的結
果發現,受磁組的細胞素 B1 和 E1 表現量上升且受磁組 ATM-NBS1-CHK 信號傳導途徑也
因磁場而活化。在次世代定序的結果發現,靜磁場主要影響了細胞移動、免疫和發育相
關基因表現。在活細胞影像分析的結果中發現,暴露於靜磁場下的癌細胞有較多細胞累
積在有絲分裂期,細胞型態較收縮且周圍突起較短,細胞的移動頻率較高,這顯示靜磁
場可能影響細胞中微管絲與機動蛋白的組合,使受磁組的細胞附著能力較差。在斑馬魚
生物毒性測試結果中也發現,靜磁場影響了黑色素的移動和生成,但控制組和受磁組於
受孕後 96 小時之生長率,以及幼魚的外型並沒有明顯差異。本研究意旨在理解靜磁場
調控的癌細胞效應,並評估利用此生物效應的特點,作為輔助性療法的潛能
摘要(英) Previous reports have demonstrated that exposure of electromagnetic force could affect
cellular physiology. Others have shown that static magnetic field (SMF) has impacts on cell
proliferation, particularly in cancer cells. Several physical parameters, such as magnetic
frequency, gradient, and magnitude, were reported to affect the biological consequences.
However, discrepancies exist between the SMF and cancer cell responses and the mechanisms
underlying the SMF-mediated effects remained largely unexplored. The main purpose of this
study is to investigate the mechanisms of SMF-mediated effects in cancer cells. Our results
showed that the exposure of SMF affected cancer cell proliferation and cell cycle distribution.
The doubling time for cells exposed to SMF was longer than that of control group. The results
of flow cytometry showed that SMF induced higher percentage of cells accumulated in the
mitotic phase compared to that of control group after 24-hour exposures (% of G2/M,SMF:
control= 5.50 : 0.25). Results of immune-fluorescent staining and western blotting found
higher expressions of cyclin B1 and cyclin E1 SMF-treated cells. Furthermore, the activation
of ATM-NBS1-CHK signaling pathway was enhanced. The results of Next Generation
Sequencing (NGS) analysis showed that the SMF primarily regulated genes involved in
functions of motility, immune and embryonic development related pathways. From the
time-lapse fluorescent microscope observations, more cancer cells exposed to SMF were
accumulated in mitotic phase. The SMF-treated cells exhibited a shrinkage phenotype, faster
motion frequency, and shorter peripheral protrusions. These observations indicate that the
v

SMF may affect polymerizations of microtubules and F-actin, as well as cell adhesion. To test
the SMF-mediated effects on development, we used zebrafish as the model and evaluated the
phenotypic alterations during development. We found that SMF exposures evidently affected
the distribution of melanin. Some embryonic malformations were also observed under SMF
treatment. However, there’s no difference on the survival ratio between SMF-treated group
and control group. The presented study helps to understand more molecular mechanisms of
the SMF-mediated effects on cancer cells. This may provide an opportunity to utilize the
features of SMF to tailor therapeutic strategy.
關鍵字(中) ★ 靜磁場
★ 鼻咽癌癌細胞
關鍵字(英) ★ static magnetic field
★ nasopharyngeal carcinoma
論文目次 目錄
中文摘要 ………………………………………………………………………… iii
英文摘要 ………………………………………………………………………… iv 誌謝 ………………………………………………………………………… vi
目錄 ………………………………………………………………………… vii
縮寫一覽表 ………………………………………………………………………… x
Chapter 1 Introduction…………………………………………………………… 1
1-1 Electromagnetic fields in nature……………………………………… 1
1-1-1 Tumor treating fields………………………………………………… 2
1-1-2 Electromagnetic field in environments……………………………… 3 1-1-3 Static magnetic field and human health……………………………… 4 1-2 Static magnetic field at the cellular level……………………………… 6
1-2-1 Static magnetic field and cellproliferation………………………… 6
1-2-2 The potential mechanisms of static magnetic field…………………… 7
Chapter 2 Materials and Methods……………………………………………… 9
2-1 Static magnetic field generated by Neodymium magnet…………… 9
2-2 Cell culture and treatment method…………………………………… 9
2-3 Cell cycle analysis…………………………………………………… 9
2-4 Time-lapse live cell imaging………………………………………… 10
2-5 Wound healing assay………………………………………………… 10
2-6 Real-time proliferation assay………………………………………… 11
2-7 Western blotting……………………………………………………… 11
2-8 Immunofluorescent staining………………………………………… 12
2-9 RNA sequencing and quantification………………………………… 12
2-9-1 RNA extraction and RNA sequencing………………………………… 12 2-9-2 Transcriptome analysis……………………………………………… 13
2-9-3 Real time quantitative polymerase chain reaction…………………… 13
2-10 Zebrafish toxicity assay……………………………………………… 14
2-11 Statistics analysis…………………………………………………… 14
Chapter 3 Results………………………………………………………………… 16
3-1 Distribution of Neodymium magnet flux…………………………… 16
3-2 SMF decreases cancer cell proliferation……………………………… 16 3-3 SMF induces cell cycle redistribution and M phase arrest…………… 17
3-4 SMF induces DNA damage response………………………………… 17
3-5 The top scoring pathways dysregulated by SMF……………………… 18
3-6 Validation of selected genes involved in cell motility………………… 18
3-7 SMF affects cell mobility…………………………………………… 19
3-8 SMF reduces melanin production and migration during development of zebrafish…………………………………………………………… 20
Chapter 4 Discussion…………………………………………………………… 21
4-1 Possible mechanisms under SMF exposures………………………… 21 4-1-1 SMF induces DNA damage response in NPC cells…………………… 21
4-1-2 SMF exposure results in M phase arrest……………………………… 22
4-1-3 SMF regulates cell proliferation………………………………… 22 4-1-4 SMF decreases the cell motility……………………………………… 23
4-1-5 Zebrafish as a model for SMF toxicity tests……………………… 24
4-2 Future perspectives…………………………………………………… 24
Figures ………………………………………………………………………… 26
Figure 1 Characterization of SMF flux………………………………………… 26
Figure 2 The vectors of SMF distribution……………………………………… 27 Figure 3 SMF decreases cancer cell proliferation…………………………… 28
Figure 4 SMF induces cell cycle redistribution and M phase arrest…………… 29
Figure 5 SMF activates DNA damage response……………………………… 30 Figure 6 The top scoring pathways dysregulated by SMF…………………… 31
Figure 7 Expression patterns of genes under SMF exposures………………… 32
Figure 8 Validation of selected genes involved in cell motility……………… 33
Figure 9 SMF affects cell mobility…………………………………………… 34
Figure 10 SMF reduces melanin production and migration during development of zebrafish…………………………………………………………… 35
Appendix Housing of zebrafish for toxicity assay………………………36
References ………………………………………………………………………… 37

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指導教授 陳健章 劉淑貞(Chien-Chang Chen Shu-Chen Liu) 審核日期 2020-1-22
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