| 研究生: |
高銘澤 Ming-Tse Kao |
|---|---|
| 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 |
| 指導教授: |
陳健章
Chien-Chang Chen 劉淑貞 Shu-Chen Liu |
| 口試委員: | |
| 學位類別: |
碩士 Master |
| 系所名稱: |
生醫理工學院 - 生物醫學工程研究所 Graduate Institute of Biomedical Engineering |
| 論文出版年: | 2020 |
| 畢業學年度: | 108 |
| 語文別: | 英文 |
| 論文頁數: | 56 |
| 中文關鍵詞: | 靜磁場 、鼻咽癌癌細胞 |
| 外文關鍵詞: | static magnetic field, nasopharyngeal carcinoma |
| 相關次數: | 點閱:18 下載:0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
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
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.
Reference
1. Zakharchenko, A., Guz, N., Laradji, A.M., Katz, E., and Minko, S. 2018. Magnetic
field remotely controlled selective biocatalysis. Nature Catalysis 1:73.
2. Wong, W., Gan, W.L., Teo, Y.K., and Lew, W.S. 2018. Interplay of cell death signaling
pathways mediated by alternating magnetic field gradient. Cell death discovery
4:49-49.
3. Colbert, A.P., Markov, M.S., and Souder, J.S. 2008. Static magnetic field therapy:
dosimetry considerations. The Journal of Alternative and Complementary Medicine
14:577-582.
4. Zhang, Y., Wei, F., Poh, Y.-C., Jia, Q., Chen, J., Chen, J., Luo, J., Yao, W., Zhou, W.,
and Huang, W. 2017. Interfacing 3D magnetic twisting cytometry with confocal
fluorescence microscopy to image force responses in living cells. Nature protocols
12:1437.
5. Bininda-Emonds, O.R., Cardillo, M., Jones, K.E., MacPhee, R.D., Beck, R.M.,
Grenyer, R., Price, S.A., Vos, R.A., Gittleman, J.L., and Purvis, A. 2007. The delayed
rise of present-day mammals. Nature 446:507.
6. Clarke, D., Whitney, H., Sutton, G., and Robert, D. 2013. Detection and learning of
floral electric fields by bumblebees. Science 340:66-69.
7. Liang, C.-H., Chuang, C.-L., Jiang, J.-A., and Yang, E.-C. 2016. Magnetic sensing
38
through the abdomen of the honey bee. Scientific reports 6:23657.
8. Foley, L.E., Gegear, R.J., and Reppert, S.M. 2011. Human cryptochrome exhibits
light-dependent magnetosensitivity. Nature communications 2:356.
9. Aragonès, A.C., Haworth, N.L., Darwish, N., Ciampi, S., Bloomfield, N.J., Wallace,
G.G., Diez-Perez, I., and Coote, M.L. 2016. Electrostatic catalysis of a Diels–Alder
reaction. Nature 531:88.
10. Mehta, M., Wen, P., Nishikawa, R., Reardon, D., and Peters, K. 2017. Critical review
of the addition of tumor treating fields (TTFields) to the existing standard of care for
newly diagnosed glioblastoma patients. Critical reviews in oncology/hematology
111:60-65.
11. Kessler, A.F., Frömbling, G.E., Gross, F., Hahn, M., Dzokou, W., Ernestus, R.-I., Löhr,
M., and Hagemann, C. 2018. Effects of tumor treating fields (TTFields) on
glioblastoma cells are augmented by mitotic checkpoint inhibition. Cell death
discovery 5:12.
12. Long, Y., Wei, H., Li, J., Yao, G., Yu, B., Ni, D., Gibson, A.L., Lan, X., Jiang, Y., and
Cai, W. 2018. Effective Wound Healing Enabled by Discrete Alternative Electric
Fields from Wearable Nanogenerators. ACS nano 12:12533-12540.
13. Stupp, R., Taillibert, S., Kanner, A., Read, W., Steinberg, D.M., Lhermitte, B., Toms,
S., Idbaih, A., Ahluwalia, M.S., and Fink, K. 2017. Effect of tumor-treating fields plus
39
maintenance temozolomide vs maintenance temozolomide alone on survival in
patients with glioblastoma: a randomized clinical trial. Jama 318:2306-2316.
14. Sienkiewicz, Z. 2013. International Workshop on Non‐Ionizing Radiation Protection
in Medicine. Medical physics 40.
15. Lu, Y., Worrell, G.A., Zhang, H.C., Yang, L., Brinkmann, B., Nelson, C., and He, B.
2014. Noninvasive imaging of the high frequency brain activity in focal epilepsy
patients. IEEE Transactions on Biomedical Engineering 61:1660-1667.
16. Brain, J.D., Kavet, R., McCormick, D.L., Poole, C., Silverman, L.B., Smith, T.J.,
Valberg, P.A., Van Etten, R., and Weaver, J.C. 2003. Childhood leukemia: electric and
magnetic fields as possible risk factors. Environmental Health Perspectives
111:962-970.
17. Tao, R., and Huang, K. 2011. Reducing blood viscosity with magnetic fields. Physical
Review E 84:011905.
18. Vallbona, C., Hazlewood, C.F., and Jurida, G. 1997. Response of pain to static
magnetic fields in postpolio patients: a double-blind pilot study. Archives of physical
medicine and rehabilitation 78:1200-1203.
19. Alfano, A.P., Taylor, A.G., Foresman, P.A., Dunkl, P.R., McConnell, G.G., Conaway,
M.R., and Gillies, G.T. 2001. Static magnetic fields for treatment of fibromyalgia: a
randomized controlled trial. The Journal of Alternative & Complementary Medicine
40
7:53-64.
20. Juhász, M., Nagy, V.L., Székely, H., Kocsis, D., Tulassay, Z., and László, J.F. 2014.
Influence of inhomogeneous static magnetic field-exposure on patients with erosive
gastritis: a randomized, self-and placebo-controlled, double-blind, single centre, pilot
study. Journal of The Royal Society Interface 11:20140601.
21. Colbert, A.P., Wahbeh, H., Harling, N., Connelly, E., Schiffke, H.C., Forsten, C.,
Gregory, W.L., Markov, M.S., Souder, J.J., and Elmer, P. 2009. Static magnetic field
therapy: a critical review of treatment parameters. Evidence-based complementary and
alternative medicine 6:133-139.
22. Polyakova, T., Zablotskii, V., and Dejneka, A. 2017. Cell membrane pore formation
and change in ion channel activity in high-gradient magnetic fields. IEEE Magnetics
Letters 8:1-5.
23. Ghibelli, L., Cerella, C., Cordisco, S., Clavarino, G., Marazzi, S., De Nicola, M.,
Nuccitelli, S., D'alessio, M., Magrini, A., and Bergamaschi, A. 2006. NMR exposure
sensitizes tumor cells to apoptosis. Apoptosis 11:359-365.
24. Fanelli, C., Coppola, S., Barone, R., Colussi, C., Gualandi, G., Volpe, P., and Ghibelli,
L. 1999. Magnetic fields increase cell survival by inhibiting apoptosis via modulation
of Ca2+ influx. The FASEB journal 13:95-102.
25. Pacini, S., Gulisano, M., Peruzzi, B., Sgambati, E., Gheri, G., Bryk, S.G., Vannucchi,
41
S., Polli, G., and Ruggiero, M. 2003. Effects of 0.2 T static magnetic field on human
skin fibroblasts. Cancer detection and prevention 27:327-332.
26. Gioia, L., Saponaro, I., Bernabo, N., Tettamanti, E., Mattioli, M., and Barboni, B.
2013. Chronic exposure to a 2 mT static magnetic field affects the morphology, the
metabolism and the function of in vitro cultured swine granulosa cells.
Electromagnetic biology and medicine 32:536-550.
27. Wang, J., Xiang, B., Deng, J., Freed, D.H., Arora, R.C., and Tian, G. 2016. Inhibition
of viability, proliferation, cytokines secretion, surface antigen expression, and
adipogenic and osteogenic differentiation of adipose-derived stem cells by seven-day
exposure to 0.5 T static magnetic fields. Stem cells international 2016.
28. Stolfa, S., Skorvanek, M., Stolfa, P., Rosocha, J., Vasko, G., and Sabo, J. 2007. Effects
of static magnetic field and pulsed electromagnetic field on viability of human
chondrocytes in vitro. Physiological research 56:S45.
29. Martino, C.F., Perea, H., Hopfner, U., Ferguson, V.L., and Wintermantel, E. 2010.
Effects of weak static magnetic fields on endothelial cells. Bioelectromagnetics:
Journal of the Bioelectromagnetics Society, The Society for Physical Regulation in
Biology and Medicine, The European Bioelectromagnetics Association 31:296-301.
30. Chuo, W., Ma, T., Saito, T., Sugita, Y., Maeda, H., Zhang, G., Li, J., Liu, J., and Lu, L.
2013. A preliminary study of the effect of static magnetic field acting on rat bone
42
marrow mesenchymal stem cells during osteogenic differentiation in vitro. Journal of
Hard Tissue Biology 22:227-232.
31. Denegre, J.M., Valles, J.M., Lin, K., Jordan, W., and Mowry, K.L. 1998. Cleavage
planes in frog eggs are altered by strong magnetic fields. Proceedings of the National
Academy of Sciences 95:14729-14732.
32. Sullivan, K., Balin, A.K., and Allen, R.G. 2011. Effects of static magnetic fields on the
growth of various types of human cells. Bioelectromagnetics 32:140-147.
33. Papatheofanis, F.J. 1990. Use of calcium channel antagonists as magnetoprotective
agents. Radiation research 122:24-28.
34. Prasad, A., Teh, D.B.L., Blasiak, A., Chai, C., Wu, Y., Gharibani, P.M., Yang, I.H.,
Phan, T.T., Lim, K.L., and Yang, H. 2017. Static magnetic field stimulation enhances
oligodendrocyte differentiation and secretion of neurotrophic factors. Scientific reports
7:6743.
35. Luo, Y., Ji, X., Liu, J., Li, Z., Wang, W., Chen, W., Wang, J., Liu, Q., and Zhang, X.
2016. Moderate intensity static magnetic fields affect mitotic spindles and increase the
antitumor efficacy of 5-FU and Taxol. Bioelectrochemistry 109:31-40.
36. Zhang, L., Wang, J., Wang, H., Wang, W., Li, Z., Liu, J., Yang, X., Ji, X., Luo, Y., and
Hu, C. 2016. Moderate and strong static magnetic fields directly affect EGFR kinase
domain orientation to inhibit cancer cell proliferation. Oncotarget 7:41527.
43
37. Kimmel, C.B., Ballard, W.W., Kimmel, S.R., Ullmann, B., and Schilling, T.F. 1995.
Stages of embryonic development of the zebrafish. Developmental dynamics
203:253-310.
38. Tajik, A., Zhang, Y., Wei, F., Sun, J., Jia, Q., Zhou, W., Singh, R., Khanna, N.,
Belmont, A.S., and Wang, N. 2016. Transcription upregulation via force-induced
direct stretching of chromatin. Nature materials 15:1287.
39. Le, H.Q., Ghatak, S., Yeung, C.-Y.C., Tellkamp, F., Günschmann, C., Dieterich, C.,
Yeroslaviz, A., Habermann, B., Pombo, A., and Niessen, C.M. 2016. Mechanical
regulation of transcription controls Polycomb-mediated gene silencing during lineage
commitment. Nature cell biology 18:864.
40. Le, Q.-H. 2016. Mechanisms of force-mediated regulation of transcription, chromatin
remodeling and cell fate decisions. Universität zu Köln