請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/81127
標題: TRIB3蛋白參與阿黴素誘導胃癌細胞的凋亡
TRIB3 involves in Doxorubicin - induced apoptosis in gastric cancer cells
作者: 吳怡瑢
Wu, I-Jung
關鍵字: TRIB3蛋白
TRIB3
阿黴素
細胞凋亡
Doxorubicin
apoptosis
出版社: 生命科學院碩士在職專班
引用: Mata, J., S. Curado, et al. (2000). "Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis." Cell 101(5): 511-522. Deloukas, P., L. H. Matthews, et al. (2001). "The DNA sequence and comparative analysis of human chromosome 20." Nature 414(6866): 865-871. Boudeau, J., D. Miranda-Saavedra, et al. (2006). "Emerging roles of pseudokinases." Trends Cell Biol 16(9): 443-452. Liew, C. W., J. Bochenski, et al. (2010). "The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells." J Clin Invest 120(8): 2876-2888. Du, K., S. Herzig, et al. (2003). "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver." Science 300(5625): 1574-1577. Wu, M., L. G. Xu, et al. (2003). "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription." J Biol Chem 278(29): 27072-27079. Kiss-Toth, E., S. M. Bagstaff, et al. (2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades." J Biol Chem 279(41): 42703-42708. Qi, L., J. E. Heredia, et al. (2006). "TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism." Science 312(5781): 1763-1766. Ohoka, N., S. Yoshii, et al. (2005). "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death." EMBO J 24(6): 1243-1255. Liu, J., W. Zhang, et al. (2012). "Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess." Am J Physiol Endocrinol Metab 303(7): E908-916. Kato, S. and K. Du (2007). "TRB3 modulates C2C12 differentiation by interfering with Akt activation." Biochem Biophys Res Commun 353(4): 933-938. Kuo, C. H., K. Morohoshi, et al. (2012). "The role of TRB3 in mast cells sensitized with monomeric IgE." Exp Mol Pathol 93(3): 408-415. Hua, F., R. Mu, et al. (2011). "TRB3 interacts with SMAD3 promoting tumor cell migration and invasion." J Cell Sci 124(Pt 19): 3235-3246. Weiss, R. B. (1992). "The anthracyclines: will we ever find a better doxorubicin?" Semin Oncol 19(6): 670-686. Fornari, F. A., J. K. Randolph, et al. (1994). "Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells." Mol Pharmacol 45(4): 649-656. Broser, F. (1966). "[The modern treatment of various forms of epileptic attacks and other symptoms of epileptic illnesses]." Nervenarzt 37(1): 25-32. Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman''s The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1243 Zhang, Y. W., J. Shi, et al. (2009). "Cardiomyocyte death in doxorubicin-induced cardiotoxicity." Arch Immunol Ther Exp (Warsz) 57(6): 435-445. Kerr, J. F., A. H. Wyllie, et al. (1972). "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics." Br J Cancer 26(4): 239-257. Bolshakov, K. V., V. E. Gmiro, et al. (2003). "Determinants of trapping block of N-methyl-d-aspartate receptor channels." J Neurochem 87(1): 56-65. Kuerbitz, S. J., B. S. Plunkett, et al. (1992). "Wild-type p53 is a cell cycle checkpoint determinant following irradiation." Proc Natl Acad Sci U S A 89(16): 7491-7495. Yonish-Rouach, E., D. Resnitzky, et al. (1991). "Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6." Nature 352(6333): 345-347. Thornberry, N. A. (1998). "Caspases: key mediators of apoptosis." Chem Biol 5(5): R97-103. Taylor, R. C., S. P. Cullen, et al. (2008). "Apoptosis: controlled demolition at the cellular level." Nat Rev Mol Cell Biol 9(3): 231-241. Ferri, K. F. and G. Kroemer (2001). "Organelle-specific initiation of cell death pathways." Nat Cell Biol 3(11): E255-263. Anelli, T. and R. Sitia (2008). "Protein quality control in the early secretory pathway." EMBO J 27(2): 315-327. Kaufman, R. J. (1999). "Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls." Genes Dev 13(10): 1211-1233.
摘要: TRIB3基因存在於果蠅及哺乳類動物細胞中,目前有研究證實TRIB3參與許多細胞內的調控,包含新陳代謝、發炎反應以及促進腫瘤細胞轉移等。我們運用TRIB3低、中、高表現量的七種胃癌細胞,以化學治療藥物Doxorubicin處理後,探討TRIB3在細胞內扮演的角色。在低表現量的胃癌細胞AGS中,我們超量表現TRIB3,讓細胞大量表現TRIB3後加入Doxorubicin,顯微鏡下觀察其細胞生長情況較為良好,利用MTS分析細胞存活率為61.4%(Vector存活率為51.2%),流式細胞儀檢測及細胞凋亡訊號結果都顯示細胞凋亡的比例降低。相反的,我們利用表現量較高的胃癌細胞TMK並降低TRIB3的表現,再加入Doxorubicin後顯微鏡下觀察其細胞生長情況較差,MTS分析細胞存率TMK siTRIB3 57%(TMK siControl:74%),流式細胞儀檢測及細胞凋亡訊號結果也都顯示細胞凋亡的比例增加。由上述結果我們推測TRIB3在胃癌細胞加入抗癌藥物後是扮演著保護細胞的角色,當TRIB3存在的情況下細胞死亡情形降低,相反的TRIB3被抑制的同時細胞死亡的情形也跟著增加,此一相關的機轉與細胞路徑目前仍不清楚,有待日後再探討。
TRIB3 gene exists in the cells of drosophila and mammalian. It has proven so far that TRIB3 has taken parts in regulating metabolism and inflammnatory responses in cells, as well as promoting cancer cell migration. In this study, we applied chemotherapy medicine Doxorubicin to seven distinct gastric cancer cells with different levels of TRIB3 to explore the role of TRIB3 in cells responding to Doxorubicin. Overexpression of TRIB3 improved cell survival and lowered apoptosis in gastric cancer cell AGS, which expresses the lower TRIB3 protein as compared to other gastric cancer cell lines, upon Doxorubicin treatment. On the contrary, knock-down of TRIB3 expression in TMK, which expresses the higher TRIB3 compared to AGS, attenuated cell growth and increased apoptosis under Doxorubicin treatment. In conjunction with the results we concluded that TRIB3 protects cells from Doxorubicin-induced apoptosis. Further experiments will be required to study the molecular events in TRIB3 against Doxorubicin-induced apoptosis.
URI: http://hdl.handle.net/11455/81127
其他識別: U0005-2106201319253500
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2106201319253500
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