請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51529完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李明學(Ming-Shyue Lee) | |
| dc.contributor.author | Yu-Han Hsia | en |
| dc.contributor.author | 夏予涵 | zh_TW |
| dc.date.accessioned | 2021-06-15T13:37:40Z | - |
| dc.date.available | 2016-02-24 | |
| dc.date.copyright | 2016-02-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2016-01-26 | |
| dc.identifier.citation | 1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64: 9-29.
2. 臺灣衛生福利部國民健康署 (2014) 民國102年主要死因分析. 3. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, et al. (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74: 2913-2921. 4. Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2: 897-909. 5. Singh D, Upadhyay G, Srivastava RK, Shankar S (2015) Recent advances in pancreatic cancer: biology, treatment, and prevention. Biochim Biophys Acta 1856: 13-27. 6. Vaccaro V, Sperduti I, Vari S, Bria E, Melisi D, et al. (2015) Metastatic pancreatic cancer: Is there a light at the end of the tunnel? World J Gastroenterol 21: 4788-4801. 7. Ishiwata T (2013) Pancreatic Ductal Adenocarcinoma: Basic and Clinical Challenges for Better Prognosis. Journal of Carcinogenesis & Mutagenesis 01: 1-2. 8. Xiao Z, Luo G, Liu C, Wu C, Liu L, et al. (2014) Molecular mechanism underlying lymphatic metastasis in pancreatic cancer. Biomed Res Int 2014: 1-15. 9. Yamada H, Hirano S, Tanaka E, Shichinohe T, Kondo S (2006) Surgical treatment of liver metastases from pancreatic cancer. HPB (Oxford) 8: 85-88. 10. Heestand GM, Murphy JD, Lowy AM (2015) Approach to Patients With Pancreatic Cancer Without Detectable Metastases. J Clin Oncol 33: 1770-1778. 11. Slidell MB, Chang DC, Cameron JL, Wolfgang C, Herman JM, et al. (2008) Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol 15: 165-174. 12. Emmanuel Buc DO, Olivier Antomarchi, Johan Gagnière, David Da Ines and Denis Pezet (2014) Resection of pancreatic ductal adenocarcinoma with synchronous distant metastasis: is it worthwhile. World Journal of Surgical Oncology 12: 1-8. 13. Neesse A, Krug S, Gress TM, Tuveson DA, Michl P (2013) Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma. Onco Targets Ther 7: 33-43. 14. Thierry Conroy, Françoise Desseigne, Marc Ychou, Olivier Bouché MD, Rosine Guimbaud, Yves Bécouarn, Antoine Adenis, Jean-Luc Raoul, Sophie Gourgou-Bourgade, Christelle de la Fouchardière, Jaafar Bennouna, Jean-Baptiste Bachet, et al. ( 2011) FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. n engl j med 364: 1817-1825. 15. Mierke CT (2013) Physical break-down of the classical view on cancer cell invasion and metastasis. Eur J Cell Biol 92: 89-104. 16. Harisi R, Jeney A (2015) Extracellular matrix as target for antitumor therapy. Onco Targets Ther 8: 1387-1398. 17. Patel LR, Camacho DF, Shiozawa Y, Pienta KJ, Taichman RS (2011) Mechanisms of cancer cell metastasis to the bone: a multistep process. Future Oncol 7: 1285-1297. 18. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161-174. 19. H. Birkedal-Hansen WGIM, 1 M. K. Bodden, L J. Windsor/, B. Birkedal-Hansen AD, J. A. Engler (1993) Matrix Metalloproteinases- A Review. Critical Reviews in Oral Biology and Medicine 4: 197-250. 20. Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16: 558-564. 21. Dan? K, Behrendt N, H?yer-Hansen G, Johnsen M, Lund LR, et al. (2005) Plasminogen activation and cancer. Thrombosis and Haemostasis: 676-681. 22. He Y, Liu XD, Chen ZY, Zhu J, Xiong Y, et al. (2007) Interaction between cancer cells and stromal fibroblasts is required for activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis. Clin Cancer Res 13: 3115-3124. 23. Lee MS (2006) Matrix-Degrading Type II Transmembrane Serine Protease Matriptase: Its Role in Cancer Development and Malignancy. J Cancer Mol 2(5): 183-190. 24. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8: 221-233. 25. Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4: 617-629. 26. Hoff PAMS-vBaJWVd (2005) Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors. BioTechniques 38: 73-83. 27. Wolfram Bode PR, Robert Huber TK, Tschesche SSaH (1994) The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity. The EMBO Journal 13: 1263-1269. 28. Eric W. Howard ECB, and Michael J. Banda (1991) Preferential inhibition of 72- and 92-kDa gelatinases by tissue inhibitor of metalloproteinases-2. THEJ OURNALO F BIOLOGICACLH EMISTRY 266: 13070-13075. 29. Shapiro SD (1998) Matrix metalloproteinase degradation of extracellular matrix biological consequences. Current Opinion in Cell Biology 10: 602-608. 30. Saarialho-Kere V-MKaU (1999) Matrix metalloproteinases and their inhibitors in tumgur growth and invasion. Ann Med 31: 34-45. 31. T.M. GRESS FM, ULLER-PILLASCH, M,. M. LERCH,H . FRIESSM., BUCHLER and G. ADLER (1995) Expression and in-situ localization of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in pancreatic cancer. Int J Cancer 62: 407-413. 32. Durlik M GK (2012) Metalloproteinase 2 and 9 activity in the development of pancreatic cancer. Pol Przegl Chir 84: 377-382. 33. Matsuyama Y, Takao S, Aikou T (2002) Comparison of matrix metalloproteinase expression between primary tumors with or without liver metastasis in pancreatic and colorectal carcinomas. J Surg Oncol 80: 105-110. 34. Yuenian E. Shi JT, Lynn Yieh, Anton Wellstein, Marc E. Lippman, and Robert B. Dickson (1993) Identification and characterization of a novel matrix-degrading protease from hormone-dependent human breast cancer cells. CANCER RESEARCH 53: 1409-1415. 35. Chen-Yong Lin J-KW, Jeff Torri, Li Dou, Qingxiang Amy Sang, and, Dickson RB (1997) Characterization of a Novel, Membrane-bound, 80-kDa Matrix-degrading Protease from Human Breast Cancer Cells. 272: 9147–9152. 36. Cao J CX, Zheng L, Geng L, Shi Z, Pao CC, Zheng S. (1997) Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. J Cancer Res Clin Oncol 123: 447-451. 37. Tanimoto H UL, Wang Y, Shigemasa K, Parmley TH,, TJ. OB ( 2001) Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention. Tumour Biol 22: 104-114. 38. Takeuchi T SM, Craik CS. ( 1999) Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. . Proc Natl Acad Sci U S A 96: 11054-11061. 39. Chungho Kim YC, Chan-Hee Kang, Moon Gyo Kim, HyoSeon Lee, Eun-Gyung Cho, and Dongeun Park (2005) Filamin is essential for shedding of the transmembrane serine protease, epithin. EMBO Rep 6: 1045-1051. 40. Lee MS KK, Benaud C, Dickson RB, Lin CY. (2005 ) Simultaneous activation and HAI-1-mediated inhibition of matriptase induced at activation foci in immortal human mammary epithelial cells. Am J Physiol Cell Physiol 288: 932-941. 41. Lee SL, Dickson RB, Lin CY (2000) Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J Biol Chem 275: 36720-36725. 42. Domoto T, Takino T, Guo L, Sato H (2012) Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase. Cancer Sci 103: 448-454. 43. Schweinitz (2009) Use of IHC and newly designed matriptase inhibitors to elucidate the role of matriptase in pancreatic ductal adenocarcinoma. International Journal of Oncology 35: 347-357. 44. Suzuki M, Kobayashi H, Kanayama N, Saga Y, Suzuki M, et al. (2004) Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J Biol Chem 279: 14899-14908. 45. Netzel-Arnett S, Currie BM, Szabo R, Lin CY, Chen LM, et al. (2006) Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation. J Biol Chem 281: 32941-32945. 46. Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR, et al. (2000) Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. J Biol Chem 275: 26333-26342. 47. Jin JS CT, Tsai WC, Sheu LF, Chiang H and Yu CP (2007) Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters. . Histol Histopathol 22: 305-309. 48. Kang JY D-FM, Ocal IT, Singh B, Lin CY,, Dickson RB RDaCR (2003) Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer. Cancer Res 63: 1101-1105. 49. Lee JW YS, Choi JJ, Lee SJ, Kim BG, Park CS, Lee JH,, Lin CY DRaBD (2005) Increased expression of matriptase is associated with histopathologic grades of cervical neoplasia. Hum Pathol 36: 626-633. 50. Riddick AC SC, Pennington CJ, Bass R, Nuttall RK,, Hogan A SK, Ellis V, Collins AT, Maitland NJ, Ball RY, DR: aE (2005) Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 92: 2171-2180. 51. Saleem M AV, Zhong W, Longley BJ, Lin CY,, Dickson RB R-SS, Jarrard DF and Mukhtar H (2006) A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1. Cancer Epidemiol Biomarkers Prev 15: 217-227. 52. Napp J, Dullin C, Muller F, Uhland K, Petri JB, et al. (2010) Time-domain in vivo near infrared fluorescence imaging for evaluation of matriptase as a potential target for the development of novel, inhibitor-based tumor therapies. Int J Cancer 127: 1958-1974. 53. H. Randhawa KK, H. Zeng,M.P. Moyer, K.M. Reindl (2013) Activation of ERK signaling and induction of colon cancer cell death by piperlongumine, Toxicol. In Vitro 27: 1626–1633. 54. Wei Li JM, Qingyong Ma, Bin Li, Liang Han, Jiangbo Liu, Qinhong Xu,, Wanxing Duan SY, Fengfei Wang, and Erxi Wu (2013 ) Resveratrol Inhibits the Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells Via Suppression of the PI-3KAktNF-κB Pathway. Curr Med Chem 20: 4185-4194. 55. Ramos S (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 18: 427-442. 56. Dhillon H, Chikara S, Reindl KM (2014) Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage. Toxicol Rep 1: 309-318. 57. Hardtner C, Multhoff G, Falk W, Radons J (2012) (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. Eur J Pharmacol 684: 36-43. 58. Li Y, Karagoz GE, Seo YH, Zhang T, Jiang Y, et al. (2012) Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50(Cdc37) complex and direct interactions with amino acids residues of Hsp90. J Nutr Biochem 23: 1617-1626. 59. Liu Q, Li J, Hartstone-Rose A, Wang J, Li J, et al. (2015) Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms. Evid Based Complement Alternat Med 2015: 1-15. 60. Li L, Leung PS (2014) Use of herbal medicines and natural products: an alternative approach to overcoming the apoptotic resistance of pancreatic cancer. Int J Biochem Cell Biol 53: 224-236. 61. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65: 1631-1652. 62. A. P. Kyriazis AAK, D. G. Scarpelli, J. Fogh, M. S. Rao, and R. Lepera (1982 ) Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics. Am J Pathol 106(2): 250-260. 63. M. LIEBER JM, W. NELSON-REES, M. KAPLAN and G. TODARO ESTABLISHMENT OF A CONTINUOUS TUMOR-CELL LINE (PANC-1) FROM A HUMAN CARCINOMA OF THE EXOCRINE PANCREAS. Int J Cancer 15: 741-747. 64. Yunis AA AG, Russin DJ. (1977) Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase. 19(1): 128-135. 65. 吳建興 (1991) 台灣鉤藤莖皮成分之研究. 國立成功大學，化學研究所，碩士論文. 66. Chai MG, Kim-Fuchs C, Angst E, Sloan EK (2013) Bioluminescent orthotopic model of pancreatic cancer progression. J Vis Exp: 1-5. 67. Roy R, Zurakowski D, Wischhusen J, Frauenhoffer C, Hooshmand S, et al. (2014) Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies. Br J Cancer 111: 1772-1779. 68. Takatomo Koshiba RH, Michihiko Wada, Yoshiharu Miyamoto, Koji Fujimoto, Jeon-Uk Lee, Ryuichiro Doi, Shigeki Arii, Masayuki Imamura (1998 ) Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma. Cancer Sci 82(4): 642-650. 69. SR Bramhall GS, J Dunn, NR Lemoine and JP Neoptolemos (1996) Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. British Journal of Cancer 73: 972-978. 70. Doerks T, Copley RR, Schultz J, Ponting CP, Bork P (2002) Systematic identification of novel protein domain families associated with nuclear functions. Genome Res 12: 47-56. 71. Fujiki H, Sueoka E, Watanabe T, Suganuma M (2015) Primary cancer prevention by green tea, and tertiary cancer prevention by the combination of green tea catechins and anticancer compounds. J Cancer Prev 20: 1-4. 72. Bigelow RL, Cardelli JA (2006) The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene 25: 1922-1930. 73. Khan N, Mukhtar H (2010) Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev 29: 435-445. 74. Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, et al. (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 10: 1199-1210; discussion 1210-1191. 75. Shimada K, Sakamoto Y, Sano T, Kosuge T (2006) Prognostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancreatic adenocarcinoma of the body and tail. Surgery 139: 288-295. 76. Mark Bloomston EEZ, and Alexander S. Rosemurgy II (2002) Matrix Metalloproteinases and Their Role in Pancreatic Cancer -A Review of Preclinical Studies and Clinical Trials. Annals of Surgical Oncology 9: 668-674. 77. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, et al. (2008) Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195: 757-762. 78. Ko AH (2015) Progress in the Treatment of Metastatic Pancreatic Cancer and the Search for Next Opportunities. J Clin Oncol 33: 1779-1786. 79. Wilhelm Schneiderhan FD, Martin Fundel, Shaoxia Zhou, Marco Siech, Cornelia Hasel, Peter Möller, Jürgen E. Gschwend, Thomas Seufferlein, Thomas Gress, Guido Adler and Max G. Bachem (2006) Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay. Journal of Cell Science 120: 512-519. 80. Girish C, Pradhan SC (2012) Indian herbal medicines in the treatment of liver diseases: problems and promises. Fundam Clin Pharmacol 26: 180-189. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51529 | - |
| dc.description.abstract | 胰腺癌是目前最惡性的癌症之一，病患之五年存活率僅達6%。胰腺癌高死亡率的主因來自其較易侵襲至淋巴或轉移至肝臟，進而導致高復發率的產生。然而，目前並沒有效的治療方法能夠去抑制胰腺癌侵襲以及轉移的發生。中草藥應用在治療各種疾病上已行之有年，其擁有低毒性及低副作用等特性，使之成為現今開發癌症藥物的一個新選擇。在先前的研究當中，我們從43種草藥萃取物當中鑑選出2種草藥 (NTU04及NTU43),發現其可以抑制肝癌細胞的侵襲力。在此篇研究當中，發現NTU04可以有效地抑制胰腺癌細胞之侵襲力，部分透過降低基質金屬蛋白酶 (MMP-2/-9) 的活性以及間質蛋白酶(matriptase)的表現及其活化。進一步的研究結果顯示，MMP-2/-9 的活性下降是由於NTU04 降低MMP-2的表現量，促進其金屬蛋白酶組織抑制因子-1 (TIMP-1)的表達或直接抑制其活性而導致。另外，透過減弱以及過量表達matriptase的方法，亦證明matriptase 確實參與在NTU04 抑制細胞侵襲的機制當中。為了找尋其中之有效成分，我們利用液相層析儀分離MSL-UH，結果顯示F3,F4含有效的成分抑制胰腺癌細胞侵襲力,在動物胰臟原位腫瘤模式的實驗當中，也看到其混和物有抑制腫瘤生長以及轉移的效果。再進ㄧ步分離F3及F4，發現F3-4, F3-5, F4-2 和F4-3相較於其它的子分層擁有較好的抑制活性。另外，我們也透過核磁共振光譜儀以及質譜分析儀鑑定出F3-4 中的主要組成為表兒茶素，但進一步分析顯示表兒茶素並非F3-4中抑制侵襲力之主要活性成份。綜和以上，NTU04 可透過抑制MMP-2/-9 以及matriptase 而達到抑制胰腺癌細胞侵襲力的效果。在一步步分離MSL-UH 之後，我們將找出可能含有抑制侵襲力之活性成分之子分層並進ㄧ步鑑選出有效成分。本篇研究顯示NTU04以及MSL-UH為具有治療轉移性胰腺癌潛力之藥物，期許未來更進ㄧ步的研究可使其成為治療胰腺癌的新選擇。 | zh_TW |
| dc.description.abstract | Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies with 6% of 5-year survival rates. The high mortality of PDAC is mainly due to high lymphatic invasion incidence, liver metastasis, and consequently high recurrence. Thus, suppression of PDAC cell invasion and metastasis will be a good strategy to slow down PDAC progression and reduce the mortality of this disease. However, there’s currently no effective therapy that can inhibit PDAC cell invasion and metastasis. Herbal extracts have been used in traditional medicine for a long time and shown with low cytotoxicity and side effects. Thus, herbal extracts may serve as good sources to isolate effective components for cancer therapy. In our previous study, from 43 herbal extracts, we found that two of them (NTU04 and NTU43) were able to inhibit HCC cell invasion with low cytotoxicity. In this study, NTU04 was found to effectively suppress PDAC cell invasion via reducing MMP-2/-9 activities, matriptase’s expression and activation. The data further showed that NTU04-reduced MMP-2/9 activities were at least via down-regulating MMP-2 expression, up-regulating tissue inhibitor of metalloprotease-1 (TIMP1) as well as by direct inhibition. On the other hand, matriptase was also proved to be involved in NTU04-inhibited cell invasion by matriptase knockdown and overexpression strategies. To further identify the effective components from the herbal extracts, we purified an herbal extract (MSL-UH) from a Taiwanese herbal species close to NTU04, and used chromatography to fractionate MSL-UH. The results showed that MSL-UH also could inhibit PDAC cell invasion and the subfractions (F3, F4) exhibited more inhibitory effects on PDAC cell invasion than the other fractions. In the orthotopic pancreatic tumor xenograft model, F3,4 mixture administration also showed to suppress tumor growth and liver metastasis. Furthermore, four subfractions (F3-4, F3-5, F4-2 and F4-3) of which were fractionated from F3 and F4 exhibited more inhibitory effects on PANC-1 cell invasion than the others. We also identified that epi-catechin is the major compound in F3-4 by NMR and LC-MS/MS. However, epi-catechin was apparently not the active compound in F3-4 for inhibiting PDAC cell invasion. These results together indicate that NTU04 and MSL-UH may exhibit some potential active components and candidate agents which will be ably against malignant metastatic PDAC cancers. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T13:37:40Z (GMT). No. of bitstreams: 1 ntu-104-R01442029-1.pdf: 5526588 bytes, checksum: 01b21f5de88c7b4892c61c1f298faa27 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | CONTENTS
致謝……………………………………………………………………………………I 摘要……………………………………………………………………………..……III Abstract……………………………………………………………………………...IV Chapter 1.Introductions 1 1.1 Pancreatic cancer 2 1.2 Cancer metastasis: focus on protease and their inhibitors 3 1.3 Herbal extracts 8 1.4 Research motivation 9 Chapter 2. Materials and Methods 11 2.1 Materials 12 2.2 Methods 16 Chapter 3. Results 32 3.1 Effects of NTU04 on PDAC cell viabilities, growth and invasive abilities. 33 3.2 Effects of NTU04 on MMP-2/-9 gelatinolytic activities in Capan-1 and PANC-1 cells. 34 3.3 Effects of NTU04 on MMP-2/-9 proteins and mRNA expressions in Capan-1 and PANC-1 cells. 35 3.4 Effects of NTU04 on TIMP-1 and TIMP-2 expression. 36 3.5 Role of TIMP-1 in NTU04-inhibited cell invasion. 36 3.6 Effects of NTU04 on the gelatinolytic activities of human recombinant MMP-9. 37 3.7 Effects of NTU04 on matriptase in PDAC cells. 38 3.8 Role of matriptase in NTU04-inhibited cell invasion 40 3.9 Effects of MSL-UH and its sub-fractions on suppressing Capan-1 and PANC-1 cell invasion. 42 3.10 Identification of effective herbal compounds or components in F3 and F4 sub-fractions. 44 3.11 Identification of major constitutions in F3-4 by NMR and LC- MS/MS. 45 3.12 To determine whether epi-catechin (EC) was a major compound in F3-4 for inhibiting PDAC cell invasion. 46 3.13 Effects of the F3,4 fraction of MSL-UH on the tumor growth of PANC-1 cells in an orthotropic mouse model. 46 Chapter 4. Discussions 49 Chapter 5. Figures 55 Chapter 6. Reference 90 LIST OF FIGURES Figure 1. Analysis of the IC50 values of NTU04 on different PDAC cells and the effect of NTU04 on PDAC cell growth and invasion. 57 Figure 2. NTU04 reduces MMP-2/-9 gelatinolytic activities in Capan-1 and PANC-1 cells. 60 Figure 3. Effects of NTU04 on the protein and mRNA expression levels of MMP-2/-9 in Capan-1 and PANC-1 cells. 62 Figure 4. NTU04 up-regulates the protein levels of TIMP-1 but not TIMP-2 and has no significant effect on their transcription. 65 Figure 5. The induction of TIMP-1 by NTU04 is partially involved in NTU04-inhibited PDAC cell invasion. 67 Figure 6. NTU04 directly inhibits MMP-9 activities. 69 Figure 7. Analysis of NTU04 effects on matriptase in PDAC cells. 72 Figure 8. Analysis of matriptase’s role in NTU04-inhibited PDAC cell invasion. 75 Figure 9. MSL-UH suppressed Capan-1 and PANC-1 cell invasion and its subfractions F3, F4 possessed better inhibitory potentials. 78 Figure 10. Fractionations of F3 to five subfractions and F4 to seven sub-fractions by HPLC. 81 Figure 11. The sub-fraction effects of F3 and F4 on PANC-1 cell invasion. 82 Figure 12. Characterization of F3-4 by NMR and LC-ESI-MS. 85 Figure 13. Examination of F3, F3-4, and F3-5 effects on MMP-9 activity. 86 Figure 14. Effects of the F3,4 fraction of MSL-UH on the tumor growth of PANC-1 cell in an orthotropic mouse model. 88 | |
| dc.language.iso | en | |
| dc.subject | 中草藥 | zh_TW |
| dc.subject | 間質蛋白? | zh_TW |
| dc.subject | 金屬蛋白?組織抑制因子-1 | zh_TW |
| dc.subject | 胰腺癌侵襲 | zh_TW |
| dc.subject | 基質金屬蛋白? | zh_TW |
| dc.subject | Matrix metalloproteinase (MMP) | en |
| dc.subject | Pancreatic ductal adenocarcinoma (PDAC) | en |
| dc.subject | Matriptase | en |
| dc.subject | Tissue inhibitor of metalloprotease-1 (TIMP-1) | en |
| dc.subject | Herbal extracts | en |
| dc.subject | Invasion | en |
| dc.title | 草藥萃取物NTU04及MSL-UH抑制胰腺癌侵襲力以及機制之研究 | zh_TW |
| dc.title | Herbal extracts NTU04 and MSL-UH suppress pancreatic ductal adenocarcinoma cell invasion via inhibiting MMP-2/-9 activities and matriptase | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林榮耀(Jung-Yaw Lin),蕭培文(Pei-Wen Hsiao),顧記華(Jih-Hwa Guh) | |
| dc.subject.keyword | 胰腺癌侵襲,中草藥,基質金屬蛋白?,金屬蛋白?組織抑制因子-1,間質蛋白?, | zh_TW |
| dc.subject.keyword | Pancreatic ductal adenocarcinoma (PDAC),Invasion,Herbal extracts,Matrix metalloproteinase (MMP),Tissue inhibitor of metalloprotease-1 (TIMP-1),Matriptase, | en |
| dc.relation.page | 97 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-01-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf 未授權公開取用 | 5.4 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。