請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24597完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林榮耀 | |
| dc.contributor.author | Ya-Yueh Pang | en |
| dc.contributor.author | 龎雅月 | zh_TW |
| dc.date.accessioned | 2021-06-08T05:32:35Z | - |
| dc.date.copyright | 2011-10-05 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-27 | |
| dc.identifier.citation | [1] H.B. El-Serag, K.L. Rudolph, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132 (2007) 2557-2576.
[2] J. Bruix, M. Sherman, Management of hepatocellular carcinoma: an update. Hepatology 53 (2011) 1020-1022. [3] E.K. Nakakura, M.A. Choti, Management of hepatocellular carcinoma. Oncology (Williston Park) 14 (2000) 1085-1098; discussion 1098-1102. [4] J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, J.F. Blanc, A.C. de Oliveira, A. Santoro, J.L. Raoul, A. Forner, M. Schwartz, C. Porta, S. Zeuzem, L. Bolondi, T.F. Greten, P.R. Galle, J.F. Seitz, I. Borbath, D. Haussinger, T. Giannaris, M. Shan, M. Moscovici, D. Voliotis, J. Bruix, Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (2008) 378-390. [5] A. Molassiotis, P. Fernadez-Ortega, D. Pud, G. Ozden, J.A. Scott, V. Panteli, A. Margulies, M. Browall, M. Magri, S. Selvekerova, E. Madsen, L. Milovics, I. Bruyns, G. Gudmundsdottir, S. Hummerston, A.M. Ahmad, N. Platin, N. Kearney, E. Patiraki, Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol 16 (2005) 655-663. [6] G.M. Cragg, D.J. Newman, Plants as a source of anti-cancer agents. J Ethnopharmacol 100 (2005) 72-79. [7] H. Yano, A. Mizoguchi, K. Fukuda, M. Haramaki, S. Ogasawara, S. Momosaki, M. Kojiro, The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res 54 (1994) 448-454. [8] A. Sun, J.S. Chia, C.P. Chiang, S.P. Hsuen, J.L. Du, C.W. Wu, W.B. Wang, The chinese herbal medicine Tien-Hsien liquid inhibits cell growth and induces apoptosis in a wide variety of human cancer cells. J Altern Complement Med 11 (2005) 245-256. [9] Z.Y. Wang, G.S. Li, H.X. Huang, [Clinical observation on treatment of 75 mid-late stage cancer patients with yanshu Injection]. Zhongguo Zhong Xi Yi Jie He Za Zhi 26 (2006) 681-684. [10] C. Qi, [Relationship between T cell subsets and traditional Chinese medicine type in patient with ovarian tumor]. Zhongguo Zhong Xi Yi Jie He Za Zhi 14 (1994) 334-336, 323. [11] Y. Sun, Q. Xu, Aqueous extract from rhizoma notopterygii reduces contact sensitivity by inhibiting lymphocyte migration via down-regulating metalloproteinase activity. Pharmacol Res 46 (2002) 333-337. [12] E. Okuyama, S. Nishimura, S. Ohmori, Y. Ozaki, M. Satake, M. Yamazaki, Analgesic component of Notopterygium incisum Ting. Chem Pharm Bull (Tokyo) 41 (1993) 926-929. [13] S. Mitsui, K. Torii, H. Fukui, K. Tsujimura, A. Maeda, M. Nose, A. Nagatsu, H. Mizukami, A. Morita, The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation. J Pharmacol Exp Ther 333 (2010) 954-960. [14] T. Zimmerman, F.J. Blanco, Inhibitors targeting the LFA-1/ICAM-1 cell-adhesion interaction: design and mechanism of action. Curr Pharm Des 14 (2008) 2128-2139. [15] C. Lawson, S. Wolf, ICAM-1 signaling in endothelial cells. Pharmacol Rep 61 (2009) 22-32. [16] L.A. Zuckerman, L. Pullen, J. Miller, Functional consequences of costimulation by ICAM-1 on IL-2 gene expression and T cell activation. J Immunol 160 (1998) 3259-3268. [17] A. van de Stolpe, P.T. van der Saag, Intercellular adhesion molecule-1. J Mol Med 74 (1996) 13-33. [18] C. Chen, C. Chou, Y. Sun, W. Huang, Tumor necrosis factor alpha-induced activation of downstream NF-kappaB site of the promoter mediates epithelial ICAM-1 expression and monocyte adhesion. Involvement of PKCalpha, tyrosine kinase, and IKK2, but not MAPKs, pathway. Cell Signal 13 (2001) 543-553. [19] W.C. Huang, S.T. Chan, T.L. Yang, C.C. Tzeng, C.C. Chen, Inhibition of ICAM-1 gene expression, monocyte adhesion and cancer cell invasion by targeting IKK complex: molecular and functional study of novel alpha-methylene-gamma-butyrolactone derivatives. Carcinogenesis 25 (2004) 1925-1934. [20] K.A. Roebuck, A. Finnegan, Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol 66 (1999) 876-888. [21] G. Voraberger, R. Schafer, C. Stratowa, Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester. J Immunol 147 (1991) 2777-2786. [22] M. Karin, The regulation of AP-1 activity by mitogen-activated protein kinases. Philos Trans R Soc Lond B Biol Sci 351 (1996) 127-134. [23] T. Jelinek, A.D. Catling, C.W. Reuter, S.A. Moodie, A. Wolfman, M.J. Weber, RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol Cell Biol 14 (1994) 8212-8218. [24] M.J. Wheelock, Y. Shintani, M. Maeda, Y. Fukumoto, K.R. Johnson, Cadherin switching. J Cell Sci 121 (2008) 727-735. [25] O. De Wever, W. Westbroek, A. Verloes, N. Bloemen, M. Bracke, C. Gespach, E. Bruyneel, M. Mareel, Critical role of N-cadherin in myofibroblast invasion and migration in vitro stimulated by colon-cancer-cell-derived TGF-beta or wounding. J Cell Sci 117 (2004) 4691-4703. [26] P. Doherty, G. Williams, E.J. Williams, CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade. Mol Cell Neurosci 16 (2000) 283-295. [27] S.D. Skaper, S.E. Moore, F.S. Walsh, Cell signalling cascades regulating neuronal growth-promoting and inhibitory cues. Prog Neurobiol 65 (2001) 593-608. [28] C.S. Theisen, J.K. Wahl, 3rd, K.R. Johnson, M.J. Wheelock, NHERF links the N-cadherin/catenin complex to the platelet-derived growth factor receptor to modulate the actin cytoskeleton and regulate cell motility. Mol Biol Cell 18 (2007) 1220-1232. [29] R.B. Hazan, G.R. Phillips, R.F. Qiao, L. Norton, S.A. Aaronson, Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 148 (2000) 779-790. [30] H. Huang, X. He, Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20 (2008) 119-125. [31] A. Niida, T. Hiroko, M. Kasai, Y. Furukawa, Y. Nakamura, Y. Suzuki, S. Sugano, T. Akiyama, DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. Oncogene 23 (2004) 8520-8526. [32] M. Perez-Moreno, E. Fuchs, Catenins: Keeping cells from getting their signals crossed. Dev Cell 11 (2006) 601-612. [33] A. Nagafuchi, Molecular architecture of adherens junctions. Curr Opin Cell Biol 13 (2001) 600-603. [34] J. Piedra, S. Miravet, J. Castano, H.G. Palmer, N. Heisterkamp, A. Garcia de Herreros, M. Dunach, p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction. Mol Cell Biol 23 (2003) 2287-2297. [35] H. Ji, J. Wang, H. Nika, D. Hawke, S. Keezer, Q. Ge, B. Fang, X. Fang, D. Fang, D.W. Litchfield, K. Aldape, Z. Lu, EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin. Mol Cell 36 (2009) 547-559. [36] G. Berx, F. van Roy, Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 1 (2009) a003129. [37] S. Elloul, M.B. Elstrand, J.M. Nesland, C.G. Trope, G. Kvalheim, I. Goldberg, R. Reich, B. Davidson, Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer 103 (2005) 1631-1643. [38] J. Colicelli, Human RAS superfamily proteins and related GTPases. Sci STKE 2004 (2004) RE13. [39] K. Wennerberg, K.L. Rossman, C.J. Der, The Ras superfamily at a glance. J Cell Sci 118 (2005) 843-846. [40] M. Parri, P. Chiarugi, Rac and Rho GTPases in cancer cell motility control. Cell Commun Signal 8 (2010) 23. [41] J.L. Bos, H. Rehmann, A. Wittinghofer, GEFs and GAPs: critical elements in the control of small G proteins. Cell 129 (2007) 865-877. [42] J. Tcherkezian, N. Lamarche-Vane, Current knowledge of the large RhoGAP family of proteins. Biol Cell 99 (2007) 67-86. [43] S.K. Mitra, D.D. Schlaepfer, Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18 (2006) 516-523. [44] D. Chodniewicz, R.L. Klemke, Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold. Biochim Biophys Acta 1692 (2004) 63-76. [45] E. Brugnera, L. Haney, C. Grimsley, M. Lu, S.F. Walk, A.C. Tosello-Trampont, I.G. Macara, H. Madhani, G.R. Fink, K.S. Ravichandran, Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 4 (2002) 574-582. [46] E. Kiyokawa, Y. Hashimoto, S. Kobayashi, H. Sugimura, T. Kurata, M. Matsuda, Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev 12 (1998) 3331-3336. [47] M.G. Tucci, G. Lucarini, D. Brancorsini, A. Zizzi, A. Pugnaloni, A. Giacchetti, G. Ricotti, G. Biagini, Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma. Br J Dermatol 157 (2007) 1212-1216. [48] T. Kamai, T. Yamanishi, H. Shirataki, K. Takagi, H. Asami, Y. Ito, K. Yoshida, Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer. Clin Cancer Res 10 (2004) 4799-4805. [49] M.T. Abraham, M.A. Kuriakose, P.G. Sacks, H. Yee, L. Chiriboga, E.L. Bearer, M.D. Delacure, Motility-related proteins as markers for head and neck squamous cell cancer. Laryngoscope 111 (2001) 1285-1289. [50] S.Y. Sun, N. Hail, Jr., R. Lotan, Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 96 (2004) 662-672. [51] G. D'Andrilli, C. Kumar, G. Scambia, A. Giordano, Cell cycle genes in ovarian cancer: steps toward earlier diagnosis and novel therapies. Clin Cancer Res 10 (2004) 8132-8141. [52] M. Macaluso, M.G. Paggi, A. Giordano, Genetic and epigenetic alterations as hallmarks of the intricate road to cancer. Oncogene 22 (2003) 6472-6478. [53] A. Arnold, A. Papanikolaou, Cyclin D1 in breast cancer pathogenesis. J Clin Oncol 23 (2005) 4215-4224. [54] D. Santini, B. Vincenzi, G. Tonini, S. Scarpa, A. Baldi, Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 9 (2003) 3215; author reply 3216. [55] I. Ikai, Y. Itai, K. Okita, M. Omata, M. Kojiro, K. Kobayashi, Y. Nakanuma, S. Futagawa, M. Makuuchi, Y. Yamaoka, Report of the 15th follow-up survey of primary liver cancer. Hepatol Res 28 (2004) 21-29. [56] R.T. Poon, S.T. Fan, C.M. Lo, C.L. Liu, J. Wong, Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235 (2002) 373-382. [57] B.M. Lichtenberger, P.K. Tan, H. Niederleithner, N. Ferrara, P. Petzelbauer, M. Sibilia, Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140 (2010) 268-279. [58] B.I. Terman, M. Dougher-Vermazen, M.E. Carrion, D. Dimitrov, D.C. Armellino, D. Gospodarowicz, P. Bohlen, Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 187 (1992) 1579-1586. [59] W.J. Nelson, R. Nusse, Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303 (2004) 1483-1487. [60] T.J. Koh, C.J. Bulitta, J.V. Fleming, G.J. Dockray, A. Varro, T.C. Wang, Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis. J Clin Invest 106 (2000) 533-539. [61] S. Etienne-Manneville, A. Hall, Rho GTPases in cell biology. Nature 420 (2002) 629-635. [62] M. Fukata, M. Nakagawa, K. Kaibuchi, Roles of Rho-family GTPases in cell polarisation and directional migration. Curr Opin Cell Biol 15 (2003) 590-597. [63] S. Huveneers, E.H. Danen, Adhesion signaling - crosstalk between integrins, Src and Rho. J Cell Sci 122 (2009) 1059-1069. [64] M.D. Schaller, J.D. Hildebrand, J.D. Shannon, J.W. Fox, R.R. Vines, J.T. Parsons, Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol 14 (1994) 1680-1688. [65] H.C. Chen, P.A. Appeddu, H. Isoda, J.L. Guan, Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem 271 (1996) 26329-26334. [66] E. Sahai, C.J. Marshall, RHO-GTPases and cancer. Nat Rev Cancer 2 (2002) 133-142. [67] Y.Y. Cha, E.O. Lee, H.J. Lee, Y.D. Park, S.G. Ko, D.H. Kim, H.M. Kim, I.C. Kang, S.H. Kim, Methylene chloride fraction of Scutellaria barbata induces apoptosis in human U937 leukemia cells via the mitochondrial signaling pathway. Clin Chim Acta 348 (2004) 41-48. [68] S.Y. Lin, J.D. Liu, H.C. Chang, S.D. Yeh, C.H. Lin, W.S. Lee, Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J Cell Biochem 84 (2002) 532-544. [69] J. Ma, N.Y. Fu, D.B. Pang, W.Y. Wu, A.L. Xu, Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Med 67 (2001) 754-757. [70] C. Rui-Chuan, S. Jin-Hua, O. Gao-Liang, C. Ke-Xia, L. Jin-Quan, X. Xiao-Guang, Induction of differentiation in human hepatocarcinoma cells by isoverbascoside. Planta Med 68 (2002) 370-372. [71] Y.H. Huang, S.H. Zhang, R.X. Zhen, X.D. Xu, Y.S. Zhen, [Asiaticoside inducing apoptosis of tumor cells and enhancing anti-tumor activity of vincristine]. Ai Zheng 23 (2004) 1599-1604. [72] P.A. Farazi, R.A. DePinho, Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6 (2006) 674-687. [73] Y. Hoshida, S. Toffanin, A. Lachenmayer, A. Villanueva, B. Minguez, J.M. Llovet, Molecular classification and novel targets in hepatocellular carcinoma: recent advancements. Semin Liver Dis 30 (2010) 35-51. [74] N. Pore, Z. Jiang, A. Gupta, G. Cerniglia, G.D. Kao, A. Maity, EGFR tyrosine kinase inhibitors decrease VEGF expression by both hypoxia-inducible factor (HIF)-1-independent and HIF-1-dependent mechanisms. Cancer Res 66 (2006) 3197-3204. [75] P.S. Steeg, Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer 3 (2003) 55-63. [76] A. Duperray, L.R. Languino, J. Plescia, A. McDowall, N. Hogg, A.G. Craig, A.R. Berendt, D.C. Altieri, Molecular identification of a novel fibrinogen binding site on the first domain of ICAM-1 regulating leukocyte-endothelium bridging. J Biol Chem 272 (1997) 435-441. [77] P. Sancho-Bru, E. Juez, M. Moreno, V. Khurdayan, M. Morales-Ruiz, J. Colmenero, V. Arroyo, D.A. Brenner, P. Gines, R. Bataller, Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells. Liver Int 30 (2010) 31-41. [78] C. Rosette, R.B. Roth, P. Oeth, A. Braun, S. Kammerer, J. Ekblom, M.F. Denissenko, Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis 26 (2005) 943-950. [79] V. Olaku, A. Matzke, C. Mitchell, S. Hasenauer, A. Sakkaravarthi, G. Pace, H. Ponta, V. Orian-Rousseau, c-Met Recruits ICAM-1 as a Co-Receptor to Compensate for the Loss of CD44 in the Cd44 Null Mice. Mol Biol Cell (2011). [80] M.T. Nieman, R.S. Prudoff, K.R. Johnson, M.J. Wheelock, N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 147 (1999) 631-644. [81] M. Sandig, E.B. Voura, V.I. Kalnins, C.H. Siu, Role of cadherins in the transendothelial migration of melanoma cells in culture. Cell Motil Cytoskeleton 38 (1997) 351-364. [82] A. Makrigiannakis, G. Coukos, M. Christofidou-Solomidou, B.J. Gour, G.L. Radice, O. Blaschuk, C. Coutifaris, N-cadherin-mediated human granulosa cell adhesion prevents apoptosis: a role in follicular atresia and luteolysis? Am J Pathol 154 (1999) 1391-1406. [83] M. Bienz, H. Clevers, Linking colorectal cancer to Wnt signaling. Cell 103 (2000) 311-320. [84] E. Hiendlmeyer, S. Regus, S. Wassermann, F. Hlubek, A. Haynl, A. Dimmler, C. Koch, C. Knoll, M. van Beest, U. Reuning, T. Brabletz, T. Kirchner, A. Jung, Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Res 64 (2004) 1209-1214. [85] K. Reiss, T. Maretzky, A. Ludwig, T. Tousseyn, B. de Strooper, D. Hartmann, P. Saftig, ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J 24 (2005) 742-752. [86] Z. Lu, G. Jiang, P. Blume-Jensen, T. Hunter, Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase. Mol Cell Biol 21 (2001) 4016-4031. [87] Y. Pan, F. Bi, N. Liu, Y. Xue, X. Yao, Y. Zheng, D. Fan, Expression of seven main Rho family members in gastric carcinoma. Biochem Biophys Res Commun 315 (2004) 686-691. [88] A. Schnelzer, D. Prechtel, U. Knaus, K. Dehne, M. Gerhard, H. Graeff, N. Harbeck, M. Schmitt, E. Lengyel, Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 19 (2000) 3013-3020. [89] T.K. Lee, K. Man, J.W. Ho, X.H. Wang, R.T. Poon, C.K. Sun, K.T. Ng, I.O. Ng, R. Xu, S.T. Fan, Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target. Carcinogenesis 26 (2005) 681-687. [90] X. Pang, L. Zhang, L. Lai, J. Chen, Y. Wu, Z. Yi, J. Zhang, W. Qu, B.B. Aggarwal, M. Liu, 1'-Acetoxychavicol acetate suppresses angiogenesis-mediated human prostate tumor growth by targeting VEGF-mediated Src-FAK-Rho GTPase-signaling pathway. Carcinogenesis 32 (2011) 904-912. [91] T. Masaki, Y. Shiratori, W. Rengifo, K. Igarashi, K. Matsumoto, M. Nishioka, Y. Hatanaka, M. Omata, Hepatocellular carcinoma cell cycle: study of Long-Evans cinnamon rats. Hepatology 32 (2000) 711-720. [92] M. Liu, N. Lang, M. Qiu, F. Xu, Q. Li, Q. Tang, J. Chen, X. Chen, S. Zhang, Z. Liu, J. Zhou, Y. Zhu, Y. Deng, Y. Zheng, F. Bi, miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells. Int J Cancer 128 (2011) 1269-1279. [93] T. Yoshida, Y. Zhang, L.A. Rivera Rosado, J. Chen, T. Khan, S.Y. Moon, B. Zhang, Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol Cancer Ther 9 (2010) 1657-1668. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24597 | - |
| dc.description.abstract | Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality with 600,000 deaths annually. HCC is usually caused by some risk factors including hepatitis virus infection, aflatoxin-B1-contaminated food and chronic alcohol consumption. Some of molecularly targeted drugs are used to treat patients with advanced HCC such as Sorafenib, Sunitinib and Brivanib. However, the recurrence rate of HCC remains high due to the metastasis ability of cancer cells. Therefore, it is an urgent issue to discover novel therapeutic agents that can inhibit tumor formation and metastasis.
In recent years, Chinese Herbal Medicines (CHMs) are widely used as alternative medicines in the treatment of cancers. Notopterygii Rhizoma (NR), one kind of CHMs, is currently used for treating various inflammatory diseases including rheumatoid arthritis and relieving pain. In the present study, we examined the inhibitory effects of three CHMs (Notopterygii Rhizoma, Gardenia Jasminoides, Je Chung Yin) on cell migration and prolferation on Hep3B cells by transwell migration assay and MTT assay. We found that the aqueous extracts of NR significantly inhibit cell proliferation and migration of HCC cells in vitro and in vivo. NR suppresses the migration activity of Hep3B cells with a medium inhibitory concentration (IC50 migration) value sixteen times lower than that of proliferation activity (IC50 cytotoxicity). In vivo efficacy of NR was measured by subcutaneous tumor xenografts and tail vein injection in NOD-SCID mice. Daily oral administration with NR significantly inhibited the growth of tumor xenografts and lung metastases. By luciferase reporter assay, NR inhibits cancer cell proliferation and migration via blocking C/EBP-mediated transcriptional regulation which leads to inhibit EGFR and VEGFR-2 downstream signaling pathways significantly. Furthermore, NR suppresses the ERK/MAPK pathway to decrease the expression of ICAM-1 as shown by quantitative real-time PCR and western blotting analysis. In addition, NR suppresses the translocation of β-catenin and Slug into the nuleus resulted in inhibiting the transcription of N-cadherin, one of the cell-cell adhesion glycoproteins. Moreover, NR diminishes the activation of Rac-1 and Cdc42, the Rho GTPase family members, as demonstrated by pull down assay. It was further demonstrated NR suppresses the activation of Rac-1 and Cdc42 via FAK/Src pathway resulting in disruption the formation of actin filaments. Besides, we observed that NR causes cell cycle G1 phase arrest in HCC cells. The treatment of NR decreases the mRNA and protein levels of Cyclin D1 through the down-regulation of β-catenin and ERK pathways, and suppresses the protein levels of CDK4, Cyclin B and CDK1 in HCC cells. Taken together, Notopterygii Rhizoma may be a potential chemotherapeutic agent for the treatment of HCC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T05:32:35Z (GMT). No. of bitstreams: 1 ntu-100-R98442030-1.pdf: 2742552 bytes, checksum: ec4c25bd1727745e7702d6026075c75e (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Contents I
List of figures V Abbreviations VII 摘要 IX Abstract XI Chapter 1. Introduction 1 1. Hepatocellular cell carcinoma (HCC) 2 2. Chinese herbal medicines (CHMs) 3 3. Notopterygii Rhizoma (NR) 3 4. ICAM-1 4 5. N-cadherin 5 6. Modulation of cell metastasis through β-catenin/Slug/N-cadherin 6 7. Rho GTPases 7 8. Cell cycle regulation 8 9. Research purpose of present investigation 9 Chapter 2. Materials and Methods 10 1. Materials 11 2. Preparation of Chinese herb medicine (CHM) 12 3. Cell culture 12 4. Cell viability assay 13 5. Transwell migration and invasion assay 13 6. Analysis of actin filaments by confocal microscopy 14 7. Flow cytometry assay 15 8. RNA extraction and reverse transcription 16 8.1 RNA extraction 16 8.2 DNase I treatment 17 8.3 Reverse transcription 18 9. Quantitative real-time PCR (Q-PCR) 18 10. GST-PBD pull down assay 19 10.1 Purification of GST-PBD from E.coli extract 19 10.2 Preparation of GST-PBD beads 20 10.3 Affinity-precipitation of GTP-bound Rac-1/Cdc42 proteins 20 11. Cell fractionation of cytoplasmic and nuclear proteins 21 12. Western blotting analysis 22 12.1 Preparation of lysate from cell culture 22 12.2 Quantification of protein concentration 23 12.3 Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) 23 12.4 Immunoblotting 26 13. Luciferase reporter assay 27 13.1 Transfection 27 13.2 Measurement of luciferase signals 28 14. Mouse xenograft assay for tumor growth and lung metastasis 28 15. Statistical analysis 30 Chapter 3. Results 31 1. Effects of 3 CHMs on cell migration and proliferation of Hep3B cells. 32 2. NR suppresses migration and invasion activity of Hep3B cells. 33 3. NR inhibits tumor metastasis in vivo 33 4. NR represses C/EBP-mediated transcription leading to blockage of the expression of EGFR and VEGFR-2. 34 5. NR inhibits the expression of ICAM-1 and N-cadherin resulting in blockage of migration of Hep3B cells. 35 6. NR promotes the disruption of actin filaments by decreasing the activation of Rac-1 and Cdc42 through Src/FAK signaling pathway. 37 7. NR suppresses the proliferation of Hep3B cells. 38 8. NR inhibits tumor growth in vivo 39 9. NR arrests the cell cycle at the G1 phase in Hep3B cells. 39 10. NR inhibits the proliferation-related genes expression to block cell proliferation of Hep3B cells. 40 Chapter 4. Discussion 41 Chapter 5. Figures 48 Chapter 6. Tables 66 Chapter 7. References 69 List of figures Figure 1. Effects of CHMs on proliferation of Hep3B cells. 49 Figure 2. Effects of CHMs on migration of Hep3B cells. 50 Figure 3. Notopterygii Rhizoma inhibits invasion activity of Hep3B cells. 51 Figure 4. Notopterygii Rhizoma inhibits tumor metastasis in vivo. 52 Figure 5. Effects of Notopterygii Rhizoma on EGFR, VEGFR2 and VEGFC expression. 53 Figure 6. Effects of Notopterygii Rhizoma on the transcription regulation of genes related to metastasis and proliferation. 54 Figure 7. Notopterygii Rhizoma inhibits C/EBP-mediated transcription. 55 Figure 8. Notopterygii Rhizoma inhibits ICAM-1 expression through the ERK pathway. 56 Figure 9. Notopterygii Rhizoma suppresses N-cadherin expression through down-regulation of β-catenin and Slug expression and interferes with translocation of β-catenin and Slug into nucleus. 58 Figure 10. Notopterygii Rhizoma decreases the activation of Rac-1 and Cdc42. 59 Figure 11. Notopterygii Rhizoma decreases the activation of Rac-1 and Cdc42 via the Src/FAK signaling pathway. 60 Figure12. Notopterygii Rhizoma promotes the disruption of actin filaments. 61 Figure 13. Notopterygii Rhizoma inhibits tumor growth in vivo. 62 Figure 14. Notopterygii Rhizoma induces G1 arrest of Hep3B cells. 63 Figure 15. Notopterygii Rhizoma inhibits the expression of proliferation-related genes. 64 Figure 16. Effects of Notopterygii Rhizoma on molecular events of cell cycle. 65 Table 1. Cytotoxicity and cell migration inhibitory activities of 3 kinds of CHMs to Hep3B cells. 67 Table 2. Specific primers for Q-PCR analysis 68 | |
| dc.language.iso | en | |
| dc.title | 羌活抑制肝癌細胞的轉移與增生 | zh_TW |
| dc.title | Notopterygii Rhizoma Suppresses the Migration and Proliferation of Hepatocellular Carcinoma Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 呂紹俊,李明學,李德章 | |
| dc.subject.keyword | 肝細胞癌,羌活,轉移,增生,C/EBP,表皮生長因子受體,血管內皮生長因子受體, | zh_TW |
| dc.subject.keyword | Hepatocellular carcinoma,Notopterygii Rhizoma,Migration,Proliferation,C/EBP,EGFR,VEGFR-2, | en |
| dc.relation.page | 77 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-07-27 | |
| 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-100-1.pdf 目前未授權公開取用 | 2.68 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。