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研究生:張毓真
研究生(外文):Yu-Chen Chang
論文名稱:肝癌病患常用中藥處方與放射治療交互作用研究
論文名稱(外文):Investigation the effects of common prescribed Chinese herbal medicine on radiotherapy for liver cancer patients
指導教授:黃正仲黃正仲引用關係
指導教授(外文):Jeng-Jong Hwang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物醫學影像暨放射科學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:31
中文關鍵詞:NF-kBHMF放射治療交互作用分子影像
外文關鍵詞:NF-kBHMFradiotherapyinteractionmolecular imaging
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癌症自1982年起即成為台灣十大死因之首,放射治療是癌症的標準療法之一。許多癌症病患在放射治療過程中服用中藥處方,但對放射治療的影響尚不清楚,可能增強或減弱放射治療的效果,故研究這些常用中藥處方與放射治療的交互作用對病患安全是很重要的。
文獻指出游離輻射會誘導細胞產生輻射抗性。本實驗室已發表的文獻指出NF-kB在誘導輻射抗性上扮演重要角色,本實驗室已建立NF-kB結合報導基因之分子影像平台,可利用分子影像來即時觀測NF-kB之表現。因此本篇論文也以NF-kB的活性評估常用中藥處方與放射治療之交互作用及機制。
在本篇論文中,以5-hydroxymethyl-2-furfural (HMF,為常見中藥藥方中的主要成分),結合已建立之NF-kB分子影像平台,研究在肝癌中,中藥成分與放射治療的交互作用,並探討其機轉。研究結果顯示,HMF可以抑制游離輻射所引起的NF-kB活性,進而抑制NF-kB的下游發炎蛋白。此外,HMF合併放射治療可增加細胞凋亡蛋白的表現,具有輻射增敏效果。綜合以上的研究結果,HMF為具有潛力的抗腫瘤中草藥物,於臨床上,可合併放射治療做為肝癌的治療方式。
Cancer has become the first mortality of the top ten causes of death since 1982 in Taiwan. More than 50% of cancer patients have been treated with radiotherapy (RT). Many patients undergoing RT also have traditional Chinese medicine, however, the influence of herbal medicine on RT is still ambiguous. Hence, to investigate the interaction between traditional Chinese medicine and RT and the underlying mechanism is important for both therapeutics and safety issues.
Many studies have shown that radioresistance can be induced by ionizing radiation, in which NF-kB plays an important role. In this study, the NF-kB promoter/firefly luciferase reporter system was used as a molecular imaging platform to detect the expression of NF-kB real time. 5-hydroxymethyl-2-furfural (HMF), the main ingredient of common traditional Chinese medicine, was used to combine radiation in human Huh7/NF-kB/tk-IRES-luc2/rfp hepatocellular carcinoma cell line to investigate the interaction between traditional Chinese medicine and RT and the underlying mechanism. The results show that HMF decreases the radiation-induced NF-B activity, and the expressions of its downstream effector proteins. Combination of radiation and HMF increases the apoptotic protein such as cleaved caspase 3, and invasive protein such as MMP-9. Taken together, these results suggest that HMF could be a potential anticancer drug, and the combined treatment of radiation and HMF may be applied as an alternative for the treatment of human hepatocellular carcinoma in clinic.

Chinese Abstract-i
English Abstract-ii
Contents-iii
List of Figures-v
Chapter 1 Introduction-1
Chapter 2 Materials and Methods-5
2.1 cell culture-5
2.2 Reagents preparation -5
2.3 Irradiation -5
2.4 Cell viability -5
2.5 NF-kB reporter assay -6
2.6 Transwell assay -7
2.7 Electrophoretic Mobility Shift Assay (EMSA) -7
2.8 Western blot analysis -8
2.9 Flow cytometric analysis -9
2.10 Statistical analysis -10
Chapter 3 Results-11
3.1 The cytotoxicity of HMF in Huh7/NF-kB/tk-IRES-luc2/rfp cells -11
3.2 HMF decreases NF-kB activity induced by radiation in Huh7/NF-kB/tk-IRES-luc2/rfp cells by NF-B reporter assay -11
3.3 HMF decreases migratory ability induced by radiation in Huh7/NF-kB/tk-IRES-luc2/rfp cells by transwell assay.-11
3.4 Combination of HMF inhibited radiation-induced NF-kB activity in Huh7/NF-kB/tk-IRES-luc2/rfp cells by EMSA -12
3.5 Proteins involved in invasion (MMP-9), proliferation (cyclinD1) are decreased, while involved in apoptosis (p-p53, p21, and cleaved caspase 3) are increased by combination of radiation with HMF in Huh7/NF-kB/tk-IRES-luc2/rfp cells assayed by Western blotting -12
3.6 G2-M phase was increased by HMF treatment in Huh7/NF-kB/tk-IRES-luc2/rfp cells. -13
Chapter 4 Discussion -14
Chapter 5 Conclusions -17
References -25
Appendices -28

List of Figures
Figure 1. The cytotoxicity of HMF in Huh7/NF-kB/tk-IRES-luc2/rfp cell.-18
Figure 2. HMF decreases radiation-induced NF-kB activity in Huh7/NF-kB/tk-IRES-luc2/rfp cells by NF-kB reporter assay.-19
Figure 3. HMF decreases migratory ability induced by radiation in Huh7/NF-kB/tk-IRES-luc2/rfp cells by transwell assay.-20
Figure 4. HMF suppresses radiation-induced NF-kB activity in Huh7/NF-kB/tk-IRES-luc2/rfp cells by EMSA.-21
Figure 5. Proteins involved in invasion (MMP-9), proliferation (cyclinD1) are decreased, while involved in apoptosis (p-p53, p21, and cleaved caspase 3) are increased by combination of radiation with HMF in Huh7/NF-kB/tk-IRES-luc2/rfp cells assayed by Western blotting.-22
Figure 6. G2-M phase was increased by HMF treatment in Huh7/NF-kB/tk-IRES-luc2/rfp cells.-23
Figure 7. Signaling pathway of radiation combined with HMF in Huh7/NF-kB/tk-IRES-luc2/rfp cells.-24

[1] Cancer registry annual reporter in Taiwan Area, Department-of-Health, (2012).
[2] Y. Zhang, J.S. Ren, J.F. Shi, N. Li, Y.T. Wang, C. Qu, Y. Zhang, M. Dai, International trends in primary liver cancer incidence from 1973 to 2007, BMC cancer, 15 (2015) 94.
[3] Y.C. Kuo, W.C. Lin, I.T. Chiang, Y.F. Chang, C.W. Chen, S.H. Su, C.L. Chen, J.J. Hwang, Sorafenib sensitizes human colorectal carcinoma to radiation via suppression of NF-kappaB expression in vitro and in vivo, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 66 (2012) 12-20.
[4] W.H. Wang, I.T. Chiang, Y.C. Liu, F.T. Hsu, H.W. Chen, C.L. Chen, Y.J. Lee, W.J. Lin, J.J. Hwang, Simultaneous imaging of temporal changes of NF-kappaB activity and viable tumor cells in Huh7/NF-kappaB-tk-luc2/rfp tumor-bearing mice, In vivo, 27 (2013) 339-350.
[5] E.C. Woodhouse, R.F. Chuaqui, L.A. Liotta, General mechanisms of metastasis, Cancer, 80 (1997) 1529-1537.
[6] S. Kim, H. Takahashi, W.W. Lin, P. Descargues, S. Grivennikov, Y. Kim, J.L. Luo, M. Karin, Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis, Nature, 457 (2009) 102-106.
[7] H.S. Rugo, The importance of distant metastases in hormone-sensitive breast cancer, Breast, 17 Suppl 1 (2008) S3-8.
[8] Y.H. Lin, K.K. Chen, J.H. Chiu, Coprescription of Chinese Herbal Medicine and Western Medications among Prostate Cancer Patients: A Population-Based Study in Taiwan, Evidence-based complementary and alternative medicine : eCAM, 2012 (2012) 147015.
[9] G. Cao, H. Cai, B. Cai, S. Tu, Effect of 5-hydroxymethylfurfural derived from processed Cornus officinalis on the prevention of high glucose-induced oxidative stress in human umbilical vein endothelial cells and its mechanism, Food chemistry, 140 (2013) 273-279.
[10] W. Li, X.N. Qu, Y. Han, S.W. Zheng, J. Wang, Y.P. Wang, Ameliorative effects of 5-hydroxymethyl-2-furfural (5-HMF) from Schisandra chinensis on alcoholic liver oxidative injury in mice, International journal of molecular sciences, 16 (2015) 2446-2457.
[11] D. Hanahan, R.A. Weinberg, The hallmarks of cancer, Cell, 100 (2000) 57-70.
[12] D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation, Cell, 144 (2011) 646-674.
[13] F. Li, G. Sethi, Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy, Biochimica et biophysica acta, 1805 (2010) 167-180.
[14] J.C. Cheng, C.H. Chou, M.L. Kuo, C.Y. Hsieh, Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway, Oncogene, 25 (2006) 7009-7018.
[15] S. Aggarwal, Y. Takada, S. Singh, J.N. Myers, B.B. Aggarwal, Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling, International journal of cancer, 111 (2004) 679-692.
[16] M.M. LoTempio, M.S. Veena, H.L. Steele, B. Ramamurthy, T.S. Ramalingam, A.N. Cohen, R. Chakrabarti, E.S. Srivatsan, M.B. Wang, Curcumin suppresses growth of head and neck squamous cell carcinoma, Clinical cancer research : an official journal of the American Association for Cancer Research, 11 (2005) 6994-7002.
[17] A.S. Baldwin, Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB, The Journal of clinical investigation, 107 (2001) 241-246.
[18] J. Li, G.K. Lau, L. Chen, S.S. Dong, H.Y. Lan, X.R. Huang, Y. Li, J.M. Luk, Y.F. Yuan, X.Y. Guan, Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression, PloS one, 6 (2011) e21816.
[19] N. Nishida, Y. Fukuda, T. Komeda, R. Kita, T. Sando, M. Furukawa, M. Amenomori, I. Shibagaki, K. Nakao, M. Ikenaga, et al., Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma, Cancer research, 54 (1994) 3107-3110.
[20] C.C. Harris, Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies, Journal of the National Cancer Institute, 88 (1996) 1442-1455.
[21] P. Fei, W.S. El-Deiry, P53 and radiation responses, Oncogene, 22 (2003) 5774-5783.

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