Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23228
標題: 引朵美洒辛誘導人類神經膠質瘤細胞凋亡的探討
Indomethacin induces apoptosis in human neuroglioma
作者: 陳盈妘
Chen, Ying-Yun
關鍵字: Indomethacin
引朵美洒辛
apoptosis
,neuroglioma
COX
細胞凋亡
神經膠質瘤
環氧化酵素
出版社: 生命科學院碩士在職專班
引用: Collins VP. 2004. Brain tumours: classification and genes. J. Neurology Neurosur. and Psychiatry 75: 112 Davies P, Bailey PJ, Goldenberg MM, Ford-Hutchinson AW. 1984. The role of arachidonic acid oxygenation products in pain and inflammation, Annu. Rev. Immunol. 2: 335-357. Deininger MH, Schluesener HJ. 1999. Cyclooxygenase-1 and -2 are differentially localized to microglia and endothelium in rat EAE and glioma. J. Neuroimmunol. 95: 202-8. DeWitt DL, Meade EA. 1993. Serum and glucocorticoid regulation of gene transcription and expression of theprostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, Arch. Biochem. Biophys. 306: 94-102. Evett GE, Xie W, Chipman JG, Robertson DL,Simmons DL. 1993. Prostaglandin G/H synthase isoenzyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens, and oncogenes, Arch. Biochem. Biophys. 306: 169-177. Fraser A, McCarthy N, Evan GI. 1996. Biochemistry of cell death. Curr. Opin. Neurobiol. 6: 71-80. Gerschenson LE, Rotello RJ. 1992. Apoptosis: a different type of cell death. FASEB. 6: 2450-5 Gould MC, Stephano JL. 2000. Inactivation of Ca2+ Action Potential Channels by the MEK Inhibitor PD98059. Exp. Cell Res. 260: 175-9. Green DR, Reed JC. 1998. Mitochondria and apoptosis. Science 281: 1309-12. Gumgumji AA, Dawood T, Parvez T. 2003. Role of COX-2 specific inhibitors in oncogenesis. J. Coll. Physicians Surg. Pak. 13: 361-5. Hla T, Ristimaki A, Appleby S, Barriocanal JG. 1993. Cyclooxygenase gene expression in inflammation and angiogenesis, Ann. N. Y. Acad. Sci. 696: 197-204. Janne PA, Mayer RJ. 2000. Chemoprevention of colorectal cancer. N. Engl. J. Med. 342:1960-8. Joki T, Heese O, Nikas DC. 2000. Expression of cyclooxygenase-2 (COX-2) in human glioma and in vitro inhibition by a specific COX- 2 inhibitor, NS-398. Cancer Res. 60: 4926-31. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM. 1993. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines, J. Biol. Chem. 268: 9049-54. Kolesnick R. 2002. The therapeutic potential of modulating the ceramide / sphingomyelin pathway. J. Clin. Invest. 110: 3-8 Kurzel F, Hagel CH, Zapf Sl. 2002. Cyclo-oxygenase inhibitors and thromboxane synthase inhibitors differentially regulate migration arrest, growth inhibition and apoptosis in human glioma cells. Acta. Neurochir. 144: 71-87. O''Sullivan MG, Chilton FH, Huggins EM, McCall CE. 1992. Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase, J. Biol. Chem. 267: 14547-50. Raff MC, Barres BA, Burne JF. 1993. Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262: 695-700 Schror K. 1993. The effect of prostaglandins and thromboxane A2 on coronary vessel tone--mechanisms of action and therapeutic implications, Eur. Heart. J. 14: 34-41. Searle J, Kerr JF, Bishop CJ. 1982. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol .Annu. 17: 229-59. Zhang GS. Zhou. GB. DC. 2004. Upregulation and activation of caspase-3 or caspase-8 and elevation of intracellular free calcium mediated apoptosis of indomethacin-induced K562 cells. Chin. Med. J. 117: 978-84. Sirois J, Simmons DL, Richards JS. 1992. Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro, J. Biol. Chem. 267: 11586-92. Simon LS. 1999. Role and regulation of cyclooxygenase-2 during inflammation. Am. J. Med. 106: 37S-42S. Smith WL, Garavito RM, DeWitt DL. 1996.Prostaglandin endoperoxide H synthase (Cyclooxygenases)-1 and -2, J. Biol. Chem. 271: 33157-60. Vane JR, Botting RM. 1998. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 47:S78-S87. Taketo M. 1998. Cyclooxygenase-2 inhibitors in tumorigenesis . J. Natl. Cancer Inst. 90:1529-36. Trifan OC, Hla T. 2003. Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis. J. Cell. Mol. Med. 7: 207-222. Wyllie AH, Beattie GJ, Hargreaves AD. 1981. Chromatin changes in apoptosis. Histochem. J. 13: 681-92.
摘要: 非類固醇抗發炎藥(NSAIDs),臨床上用於減少病人因發炎引起的疼痛,其主要功能為抑制環氧化酵素(COX)的活性,進而抑制前列腺素的生成。近來發現,一些惡性腫瘤中COX-2高度的表現可能與癌細胞生長與癌形成有關。為了解非類固醇抗發炎藥對細胞存活率的影響,本實驗利用數種不同的非類固醇抗發炎藥處理H4人類神經膠質瘤細胞,其中引朵美洒辛(indomethacin)最顯著降低H4人類神經膠質瘤細胞的存活率,其他同條件下的藥物處理對H4人類神經膠質瘤細胞的存活率並無明顯的變化。經引朵美洒辛處理的細胞會出現Annexin V染色性、去氧核醣核酸斷裂片段及凋亡細胞群,這些都顯示引朵美洒辛處理會造成細胞凋亡。在引朵美洒辛處理的細胞中可見細胞凋亡酵素8(caspase-8)及細胞凋亡酵素3(caspase-3)活化與AKT及ERK蛋白磷酸化的減少並呈現濃度與時間依賴性。以上結果顯示引朵美洒辛可能是降低H4人類神經膠質瘤細胞抗凋亡的能力而誘發細胞凋亡。藥理學上顯示添加PD98059(MEK抑制劑)、PMA (PKC活化劑)於引朵美洒辛處理細胞中具有保護作用。綜合以上實驗結果,引朵美洒辛可造成H4人類神經膠質瘤細胞典型的細胞凋亡特徵且額外添加PD98059或PMA於引朵美洒辛處理H4人類神經膠質瘤細胞具有保護作用,但其抗凋亡機制應更進一步的探討。
NSAIDs are used as a treatment for patient pain reduction from inflammatory reaction in clinic. The main function of NSAIDs is to inhibit COX activity leading to reduction of prostaglandin production. Increasing evidence shows that highly expression of COX-2 is associated with tumor cell growth and tumorgenesis in some malignancy tumors. To elicit the effect of NSAIDs on cell viability, H4 human neuroglioma cells were treated with several NSAIDs. Among these drugs, indomethacin particularly reduced H4 cell viability. Indomethacin-treated cell was accompanied by the occurrence of Annexin Ⅴ staining, DNA fragmentation and subG1 cell population, indicating the involvement of apoptotic cell death. Within the indomethacin-treated cell, the increase of active caspase-8 and caspase-3, decline of AKT phosphorylation and ERK1/2 phosphorylation were occurred in a time- and dose-dependent manner. These findings indicate that indomethacin-induced apoptotic cell death was associated with downregulation of anti-apoptotic ability. Pharmacological assay revealed the protective effects of PD98059 (a MEK inhibitor) and PMA (a PKC activator) against indomethacin-induced H4 cell viability decrease. Taken together , these findings suggest that indomethacin induced typically apoptotic characteristics in H4 cells and the anti-apoptotic mechanism of addition PD98059 or PMA in indomethacin-treated cells should be further studied.
URI: http://hdl.handle.net/11455/23228
其他識別: U0005-2408200617351700
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2408200617351700
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