請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57255
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李心予(Hsinyu Lee) | |
dc.contributor.author | Chu-Cheng Lin | en |
dc.contributor.author | 林居正 | zh_TW |
dc.date.accessioned | 2021-06-16T06:39:24Z | - |
dc.date.available | 2019-08-01 | |
dc.date.copyright | 2014-08-01 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-30 | |
dc.identifier.citation | 1] A. Plata Bello, T. Concepcion Masip, Prostate cancer epidemiology, Arch Esp Urol 67 (2014) 373-382.
[2] M.M. Center, A. Jemal, J. Lortet-Tieulent, E. Ward, J. Ferlay, O. Brawley, F. Bray, International variation in prostate cancer incidence and mortality rates, Eur Urol 61 (2012) 1079-1092. [3] M. Arya, S.R. Bott, I.S. Shergill, H.U. Ahmed, M. Williamson, H.R. Patel, The metastatic cascade in prostate cancer, Surg Oncol 15 (2006) 117-128. [4] A.M. Byrne, D.J. Bouchier-Hayes, J.H. Harmey, Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF), J Cell Mol Med 9 (2005) 777-794. [5] J.L. Su, C.J. Yen, P.S. Chen, S.E. Chuang, C.C. Hong, I.H. Kuo, H.Y. Chen, M.C. Hung, M.L. Kuo, The role of the VEGF-C/VEGFR-3 axis in cancer progression, Br J Cancer 96 (2007) 541-545. [6] Y. Zeng, K. Opeskin, L.G. Horvath, R.L. Sutherland, E.D. Williams, Lymphatic vessel density and lymph node metastasis in prostate cancer, Prostate 65 (2005) 222-230. [7] Y. Zeng, K. Opeskin, M.E. Baldwin, L.G. Horvath, M.G. Achen, S.A. Stacker, R.L. Sutherland, E.D. Williams, Expression of vascular endothelial growth factor receptor-3 by lymphatic endothelial cells is associated with lymph node metastasis in prostate cancer, Clin Cancer Res 10 (2004) 5137-5144. [8] E. Brakenhielm, J.B. Burton, M. Johnson, N. Chavarria, K. Morizono, I. Chen, K. Alitalo, L. Wu, Modulating metastasis by a lymphangiogenic switch in prostate cancer, Int J Cancer 121 (2007) 2153-2161. [9] J.B. Burton, S.J. Priceman, J.L. Sung, E. Brakenhielm, D.S. An, B. Pytowski, K. Alitalo, L. Wu, Suppression of prostate cancer nodal and systemic metastasis by blockade of the lymphangiogenic axis, Cancer Res 68 (2008) 7828-7837. 18 [10] L. Khandrika, B. Kumar, S. Koul, P. Maroni, H.K. Koul, Oxidative stress in prostate cancer, Cancer Lett 282 (2009) 125-136. [11] G. Gupta-Elera, A.R. Garrett, R.A. Robison, K.L. O'Neill, The role of oxidative stress in prostate cancer, Eur J Cancer Prev 21 (2012) 155-162. [12] B. Kumar, S. Koul, L. Khandrika, R.B. Meacham, H.K. Koul, Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype, Cancer Res 68 (2008) 1777-1785. [13] A. Laurent, C. Nicco, C. Chereau, C. Goulvestre, J. Alexandre, A. Alves, E. Levy, F. Goldwasser, Y. Panis, O. Soubrane, B. Weill, F. Batteux, Controlling tumor growth by modulating endogenous production of reactive oxygen species, Cancer Res 65 (2005) 948-956. [14] Y.J. Lee, D.M. Lee, C.H. Lee, S.H. Heo, S.Y. Won, J.H. Im, M.K. Cho, H.S. Nam, S.H. Lee, Suppression of human prostate cancer PC-3 cell growth by N-acetylcysteine involves over-expression of Cyr61, Toxicol In Vitro 25 (2011) 199-205. [15] A.M. Sanchez, S. Malagarie-Cazenave, N. Olea, D. Vara, A. Chiloeches, I. Diaz-Laviada, Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation, Apoptosis 12 (2007) 2013-2024. [16] A.A. Powolny, S.V. Singh, Plumbagin-induced apoptosis in human prostate cancer cells is associated with modulation of cellular redox status and generation of reactive oxygen species, Pharm Res 25 (2008) 2171-2180. [17] K.Y. Kim, S.N. Yu, S.Y. Lee, S.S. Chun, Y.L. Choi, Y.M. Park, C.S. Song, B. Chatterjee, S.C. Ahn, Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization, Biochem Biophys Res Commun 413 (2011) 80-86. [18] W. Lee, K.Y. Kim, S.N. Yu, S.H. Kim, S.S. Chun, J.H. Ji, H.S. Yu, S.C. Ahn, 19 Pipernonaline from Piper longum Linn. induces ROS-mediated apoptosis in human prostate cancer PC-3 cells, Biochem Biophys Res Commun 430 (2013) 406-412. [19] S. Kariya, K. Sawada, T. Kobayashi, T. Karashima, T. Shuin, A. Nishioka, Y. Ogawa, Combination treatment of hydrogen peroxide and X-rays induces apoptosis in human prostate cancer PC-3 cells, Int J Radiat Oncol Biol Phys 75 (2009) 449-454. [20] J.W. Choi, D.R. Herr, K. Noguchi, Y.C. Yung, C.W. Lee, T. Mutoh, M.E. Lin, S.T. Teo, K.E. Park, A.N. Mosley, J. Chun, LPA receptors: subtypes and biological actions, Annu Rev Pharmacol Toxicol 50 (2010) 157-186. [21] Y. Xie, T.C. Gibbs, Y.V. Mukhin, K.E. Meier, Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells, J Biol Chem 277 (2002) 32516-32526. [22] C.L. Chang, J.J. Liao, W.P. Huang, H. Lee, Lysophosphatidic acid inhibits serum deprivation-induced autophagy in human prostate cancer PC-3 cells, Autophagy 3 (2007) 268-270. [23] T.C. Gibbs, M.V. Rubio, Z. Zhang, Y. Xie, K.R. Kipp, K.E. Meier, Signal transduction responses to lysophosphatidic acid and sphingosine 1-phosphate in human prostate cancer cells, Prostate 69 (2009) 1493-1506. [24] Y. Hasegawa, M. Murph, S. Yu, G. Tigyi, G.B. Mills, Lysophosphatidic acid (LPA)-induced vasodilator-stimulated phosphoprotein mediates lamellipodia formation to initiate motility in PC-3 prostate cancer cells, Mol Oncol 2 (2008) 54-69. [25] F. Hao, M. Tan, X. Xu, J. Han, D.D. Miller, G. Tigyi, M.Z. Cui, Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha, Biochim Biophys Acta 1771 (2007) 883-892. [26] Y.S. Hwang, J.C. Hodge, N. Sivapurapu, P.F. Lindholm, Lysophosphatidic acid stimulates PC-3 prostate cancer cell Matrigel invasion through activation of RhoA and NF-kappaB activity, Mol Carcinog 45 (2006) 518-529. [27] G.V. Raj, J.A. Sekula, R. Guo, J.F. Madden, Y. Daaka, Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB, Prostate 61 (2004) 105-113. [28] P.F. Kue, J.S. Taub, L.B. Harrington, R.D. Polakiewicz, A. Ullrich, Y. Daaka, Lysophosphatidic acid-regulated mitogenic ERK signaling in androgen-insensitive prostate cancer PC-3 cells, Int J Cancer 102 (2002) 572-579. [29] C.L. Chang, M.E. Lin, H.Y. Hsu, C.L. Yao, S.M. Hwang, C.Y. Pan, C.Y. Hsu, H. Lee, Lysophosphatidic acid-induced interleukin-1 beta expression is mediated through Gi/Rho and the generation of reactive oxygen species in macrophages, J Biomed Sci 15 (2008) 357-363. [30] Q. Chen, N. Olashaw, J. Wu, Participation of reactive oxygen species in the lysophosphatidic acid-stimulated mitogen-activated protein kinase kinase activation pathway, J Biol Chem 270 (1995) 28499-28502. [31] J.M. Cunnick, J.F. Dorsey, T. Standley, J. Turkson, A.J. Kraker, D.W. Fry, R. Jove, J. Wu, Role of tyrosine kinase activity of epidermal growth factor receptor in the lysophosphatidic acid-stimulated mitogen-activated protein kinase pathway, J Biol Chem 273 (1998) 14468-14475. [32] J. Du, C. Sun, Z. Hu, Y. Yang, Y. Zhu, D. Zheng, L. Gu, X. Lu, Lysophosphatidic acid induces MDA-MB-231 breast cancer cells migration through activation of PI3K/PAK1/ERK signaling, PLoS One 5 (2010) e15940. [33] C.E. Lin, S.U. Chen, C.C. Lin, C.H. Chang, Y.C. Lin, Y.L. Tai, T.L. Shen, H. Lee, Lysophosphatidic acid enhances vascular endothelial growth factor-C expression in human prostate cancer PC-3 cells, PLoS One 7 (2012) e41096. [34] L. Zeng, S.V. Webster, P.M. Newton, The biology of protein kinase C, Adv Exp Med Biol 740 (2012) 639-661. [35] J. Kim, T. Koyanagi, D. Mochly-Rosen, PKCdelta activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells, Prostate 71 (2011) 946-954. [36] J. Kwan, H. Wang, S. Munk, L. Xia, H.J. Goldberg, C.I. Whiteside, In high glucose protein kinase C-zeta activation is required for mesangial cell generation of reactive oxygen species, Kidney Int 68 (2005) 2526-2541. [37] L. Xia, H. Wang, S. Munk, J. Kwan, H.J. Goldberg, I.G. Fantus, C.I. Whiteside, High glucose activates PKC-zeta and NADPH oxidase through autocrine TGF-beta1 signaling in mesangial cells, Am J Physiol Renal Physiol 295 (2008) F1705-1714. [38] G. Xi, X. Shen, L.A. Maile, C. Wai, K. Gollahon, D.R. Clemmons, Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCzeta-dependent manner in vascular smooth muscle cells, Diabetes 61 (2012) 104-113. [39] J.F. Di Mari, R.C. Mifflin, P.A. Adegboyega, J.I. Saada, D.W. Powell, IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is dependent on a PKCzeta-ROS pathway, Gastroenterology 124 (2003) 1855-1865. [40] J.A. Saunders, L.C. Rogers, C. Klomsiri, L.B. Poole, L.W. Daniel, Reactive oxygen species mediate lysophosphatidic acid induced signaling in ovarian cancer cells, Free Radic Biol Med 49 (2010) 2058-2067. [41] C.I. Lin, C.N. Chen, M.T. Huang, S.J. Lee, C.H. Lin, C.C. Chang, H. Lee, Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB activation- and EGFR transactivation-dependent mechanisms, Cell Signal 20 (2008) 1804-1814. [42] H.B. Lee, M.R. Yu, J.S. Song, H. Ha, Reactive oxygen species amplify protein kinase C signaling in high glucose-induced fibronectin expression by human peritoneal mesothelial cells, Kidney Int 65 (2004) 1170-1179. [43] V. Giambra, C.R. Jenkins, H. Wang, S.H. Lam, O.O. Shevchuk, O. Nemirovsky, C. Wai, S. Gusscott, M.Y. Chiang, J.C. Aster, R.K. Humphries, C. Eaves, A.P. Weng, NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-theta and reactive oxygen species, Nat Med 18 (2012) 1693-1698. [44] B. Marengo, C. De Ciucis, R. Ricciarelli, M. Passalacqua, M. Nitti, J.M. Zingg, U.M. Marinari, M.A. Pronzato, C. Domenicotti, PKCdelta sensitizes neuroblastoma cells to L-buthionine-sulfoximine and etoposide inducing reactive oxygen species overproduction and DNA damage, PLoS One 6 (2011) e14661. [45] M. Nitti, A.L. Furfaro, C. Cevasco, N. Traverso, U.M. Marinari, M.A. Pronzato, C. Domenicotti, PKC delta and NADPH oxidase in retinoic acid-induced neuroblastoma cell differentiation, Cell Signal 22 (2010) 828-835. [46] O. Bossi, M. Gartsbein, M. Leitges, T. Kuroki, S. Grossman, T. Tennenbaum, UV irradiation increases ROS production via PKCdelta signaling in primary murine fibroblasts, J Cell Biochem 105 (2008) 194-207. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57255 | - |
dc.description.abstract | 前列腺癌是男性最常罹患的癌症之一,其淋巴轉移以及荷爾蒙治療後的癌症復發 是兩個治療前列腺癌的嚴重問題,PC-3 是一種適合用來研究後期前列腺癌細胞行為的癌細胞株。水解磷酸脂 (LPA) 是一種能調控多種細胞行為的傳訊脂質,已知會促進癌細胞的生長、移動以及附著的能力。本實驗室先前於 PC-3 的研究指出, LPA 可以藉由引發過氧化物 (ROS) 生成去提高淋巴管新生因子 (VEGF-C) 的表現。 本研究以流式細胞儀以及 ROS 的染劑進行行其相對量測定,結果顯示 LPA 能在十分鐘內引發 ROS 生成,這個現象經由 NADPH oxidase (Nox) 的酵素系統所調控。利用 RNA 干擾的實驗我們證明了水解磷酸脂受器 1 和 3 (LPA1 及 LPA3) 參與這條 LPA 所調控的分子路徑。由抑制劑與 RNA 干擾的實驗也證明了磷脂酶 C (PLC) 和蛋白質激酶 C (PKC) 同樣參與 LPA 引發的 ROS 生成,而並不是經由環氧化酶 2 與內皮生長因子受器的相關傳訊路徑。於本研究中,我們發現 LPA 可以引發 PC-3 細胞中 ROS 的生成,且有 PLC/PKC/Nox 等酵素參與此路徑。 | zh_TW |
dc.description.abstract | Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA1 and LPA3 siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation, but COX-2 and EGFR are not involved in this pathway. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T06:39:24Z (GMT). No. of bitstreams: 1 ntu-103-R01b41010-1.pdf: 2631722 bytes, checksum: e098adadfc8815b81caaebbfafaccfe4 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 誌謝.................................................................................................i
中文摘要..........................................................................................ii ABSTRACT......................................................................................iii CONTENT.......................................................................................iv INTRODUCTION...............................................................................1 Prostate cancer, lymphangiogenesis and metastasis.........................1 Reactive oxygen species (ROS) and prostate cancer..........................3 Lysophosphatidic acid (LPA) and prostate cancer..............................4 Protein kinase C (PKC) and ROS........................................................5 MATERIALS AND METHODS..............................................................6 Cell culture......................................................................................6 LPA stimulation and drug treatment.................................................6 Small interfering (si) RNA transfection..............................................6 Reverse transcription (RT) and Real-time PCR..................................7 Flow cytometry................................................................................8 Statistical Analysis...........................................................................9 RESULTS........................................................................................10 LPA induces ROS generation in PC-3 cells......................................10 LPA-induced ROS generation is LPA1- and LPA3-dependent in PC-3 cells...............................................................................................11 LPA induces ROS generation through PLC in PC-3 cells...................12 LPA induces ROS generation by activating PKC in PC-3 cells............13 DISCUSSION....................................................................................14 REFERENCES....................................................................................18 FIGURES..........................................................................................24 FIGURE 1.........................................................................................24 FIGURE 2.........................................................................................26 FIGURE 3.........................................................................................28 FIGURE 4.........................................................................................30 FIGURE 5.........................................................................................32 APPENDIX: Lysophosphatidic acid induces reactive oxygen species generation by activationg protein kinase C in PC-3 human prostate cancer cells................................................................................................33 | |
dc.language.iso | zh-TW | |
dc.title | 水解磷酸脂於前列腺癌細胞引發過氧化物生成機制之研究 | zh_TW |
dc.title | Lysophosphatidic Acid induces Reactive Oxygen Species Generation by activating Protein Kinase C in PC-3 Human Prostate Cancer Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳俊宏(Jiun-Hong Chen),李明學(Ming-Shyue Lee),林赫(Ho Lin) | |
dc.subject.keyword | 水解磷酸脂,過氧化物,磷脂? C,蛋白質激? C,前列腺癌, | zh_TW |
dc.subject.keyword | LPA,ROS,PLC,PKC,prostate cancer, | en |
dc.relation.page | 38 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-07-30 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
顯示於系所單位: | 生命科學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 2.57 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。