跳到主要內容

臺灣博碩士論文加值系統

(3.235.227.117) 您好!臺灣時間:2021/08/01 22:06
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:張淑玲
研究生(外文):Shu-Ling Chang
論文名稱:茄邊鹼對膀胱癌細胞促進凋亡機制之探討
論文名稱(外文):The Pro-apoptotic Activity of Solamargine on Bladder Cancer Cells
指導教授:周寬基周寬基引用關係
指導教授(外文):Kuan-Chih Chow
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學院碩士在職專班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:36
中文關鍵詞:茄邊鹼膀胱癌細胞株
外文關鍵詞:solamarginebladder cancerJ82
相關次數:
  • 被引用被引用:0
  • 點閱點閱:299
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
癌症是目前侵襲人類健康導致死亡一個主要因素,研發各種抗癌藥物是眾多學者努力研究的方向。許多的抗癌藥物,都具備誘發腫瘤細胞-自然凋亡的作用。而中草藥是發展抗癌藥物的一個重要的來源,如黃水茄萃取液對於人類肺癌、乳癌及肝癌細胞株有極佳的抑制效果。
本研究是利用J82癌細胞株為研究題材,來探討黃水茄(Solamargine),對於抑制-膀胱癌的毒殺效果與機制。由MTT實驗結果顯示,黃水茄對J82細胞株有劑量上依賴性的抑制生長情況,其半毒殺劑量為14.77ppm。膀胱癌細胞株J82以黃水茄作用後與細胞膜上TRADD、FADD結合後,誘發產生細胞內一連串Caspase 8、Caspase 3的增加;導致細胞凋亡,另外黃水茄又促使抑制細胞進行有絲分裂之細胞核內p27、p21等蛋白的表現量。由此結果推論黃水茄藉由使膀胱癌細胞進行細胞凋亡及抑制細胞分裂而達到抗癌的效果。
Solamargine is a major steroidal alkaloid glycoside that was purified from Solanum incanum plant. Solamargine displayed a superior cytotoxicity in human lung, breast and liver cancer cells. In this study, we characterized its mechanism and showed that Solamargine induces apoptosis of the bladder cancer cells. The half-inhibitory concentration (IC50) of the cell viability assay for bladder tumor cell line, J82 cells, was 14.77 ppm. Solamargine induced apoptosis was dose-dependent and increased the sub-G1 fraction when J82 cells were examined by flow cytometry. Solamargine up-regulated the expressions of external death receptors, such as TNFR-I-associated death domain (TRADD), and Fas-associated death domain (FADD). These effects resulted in the release of mitochondrial cytochrome c and activation of caspase-8 and -3 in the cells. Solamargine also increased protein expression of p27 and p21, which mediated cell cycle arrest, in the nucleus . These results indicated that Solamargine treatment inhibited cell growth by triggering extrinsic apoptotic pathway and cell cycle arrest of bladder cancer cells.
摘要(中文)…………………………………………………………i
Abstract………………………………ii
目次………………………………………………………………iii
圖表目次…………………………………………………………iv
第一章 緒論……………………………………………………1
一、膀胱癌(Bladder cancer)……………………………1
(一)膀胱癌腫類……………………………………………1
(二)膀胱癌的原因…………………………………………2
(三)膀胱癌的症狀…………………………………………2
二、細胞週期 (cell cycle)……………………………2
三、細胞凋亡 (Apoptosis)………………………………5
四、黃水茄…………………………………………………8
五、茄邊鹼 (Solamargine)………………………………8
五、研究動機與目標………………………………………8
第二章 材料與方法……………………………………………10
一、細胞活性率測試(MTT assay)……………………………10
二、流式細胞儀分析(Flowcytometry assay)……………11
三、西方墨點法(Western Blot)……………………………12
第三章 結果………………………………………………………16
一、以細胞活性偵測Solamargine對J82細胞株的抑制生長情形…………16
二、以流式細胞儀分析法分析Solamargine對J82細胞株在細胞凋亡、細胞週期及細胞內蛋白質的表現……………………………16
三、以西方墨點法偵測Solamargine對J82細胞株蛋白的表現…………17
第四章 討論………………………………………………………18
第五章 結論………………………………………………………21
第六章 圖表………………………………………………………22
第七章 參考文獻…………………………………………………32
附錄…………………………………………………………………37
1. Liang, C.H., et al., Solamargine enhances HER2 expression and increases the susceptibility of human lung cancer H661 and H69 cells to trastuzumab and epirubicin. Chem Res Toxicol, 2008. 21(2): p. 393-9.
2. Liang, C.H., et al., Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Mol Nutr Food Res, 2007. 51(8): p. 999-1005.
3. Liang, C.H., et al., Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. Biochem Biophys Res Commun, 2004. 322(3): p. 751-8.
4. Liu, L.F., et al., Action of solamargine on human lung cancer cells--enhancement of the susceptibility of cancer cells to TNFs. FEBS Lett, 2004. 577(1-2): p. 67-74.
5. Hsu, S.H., et al., Solamargine purified from Solanum incanum Chinese herb triggers gene expression of human TNFR I which may lead to cell apoptosis. Biochem Biophys Res Commun, 1996. 229(1): p. 1-5.
6. Kuo, K.W., et al., Anticancer activity evaluation of the solanum glycoalkaloid solamargine. Triggering apoptosis in human hepatoma cells. Biochem Pharmacol, 2000. 60(12): p. 1865-73.
7. Chang, L.C., et al., The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochem Biophys Res Commun, 1998. 242(1): p. 21-5.
8. Shiu, L.Y., et al., Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin. Food Chem Toxicol, 2007. 45(11): p. 2155-64.
9. Oku, T., et al., Functional sites of human PCNA which interact with p21 (Cip1/Waf1), DNA polymerase delta and replication factor C. Genes Cells, 1998. 3(6): p. 357-69.
10. Tsurimoto, T., PCNA binding proteins. Front Biosci, 1999. 4: p. D849-58.
11. Orford, K., C.C. Orford, and S.W. Byers, Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest. J Cell Biol, 1999. 146(4): p. 855-68.
12. Peifer, M., Cell adhesion and signal transduction: the Armadillo connection. Trends Cell Biol, 1995. 5(6): p. 224-9.
13. Morin, P.J., beta-catenin signaling and cancer. Bioessays, 1999. 21(12): p. 1021-30.
14. Aubry, J.P., et al., Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry, 1999. 37(3): p. 197-204.
15. Koopman, G., et al., Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood, 1994. 84(5): p. 1415-20.
16. Vermes, I., et al., A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods, 1995. 184(1): p. 39-51.
17. Adderley, S.R. and D.J. Fitzgerald, Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. J Biol Chem, 1999. 274(8): p. 5038-46.
18. Celis, J.E. and A. Celis, Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase. Proc Natl Acad Sci U S A, 1985. 82(10): p. 3262-6.
19. Celis, J.E. and P. Madsen, Increased nuclear cyclin/PCNA antigen staining of non S-phase transformed human amnion cells engaged in nucleotide excision DNA repair. FEBS Lett, 1986. 209(2): p. 277-83.
20. Mathews, M.B., et al., Identity of the proliferating cell nuclear antigen and cyclin. Nature, 1984. 309(5966): p. 374-6.
21. Liu, S., W.R. Bishop, and M. Liu, Differential effects of cell cycle regulatory protein p21(WAF1/Cip1) on apoptosis and sensitivity to cancer chemotherapy. Drug Resist Updat, 2003. 6(4): p. 183-95.
22. Conacci-Sorrell, M., J. Zhurinsky, and A. Ben-Ze''ev, The cadherin-catenin adhesion system in signaling and cancer. J Clin Invest, 2002. 109(8): p. 987-91.
23. Cagatay, T. and M. Ozturk, P53 mutation as a source of aberrant beta-catenin accumulation in cancer cells. Oncogene, 2002. 21(52): p. 7971-80.
24. Berneburg, M., et al., ''To repair or not to repair - no longer a question'': repair of mitochondrial DNA shielding against age and cancer. Exp Dermatol, 2006. 15(12): p. 1005-15.
25. Cho, N.H., Y.T. Kim, and J.W. Kim, Correlation between G1 cyclins and HPV in the uterine cervix. Int J Gynecol Pathol, 1997. 16(4): p. 339-47.
26. Cooper, M.J., et al., p53 mutations in bladder carcinoma cell lines. Oncol Res, 1994. 6(12): p. 569-79.
27. el-Deiry, W.S., et al., WAF1, a potential mediator of p53 tumor suppression. Cell, 1993. 75(4): p. 817-25.
28. Giles, G.I., The redox regulation of thiol dependent signaling pathways in cancer. Curr Pharm Des, 2006. 12(34): p. 4427-43.
29. Gottlieb, T.M. and M. Oren, p53 and apoptosis. Semin Cancer Biol, 1998. 8(5): p. 359-68.
30. Greenblatt, M.S., et al., Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 1994. 54(18): p. 4855-78.
31. Harper, J.W., et al., The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell, 1993. 75(4): p. 805-16.
32. Jiang, H., et al., Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene, 1995. 11(12): p. 2477-86.
33. Justo, P., et al., Intracellular mechanisms of cyclosporin A-induced tubular cell apoptosis. J Am Soc Nephrol, 2003. 14(12): p. 3072-80.
34. Liang, Y., et al., Early events in Bcl-2-enhanced apoptosis. Apoptosis, 2003. 8(6): p. 609-16.
35. Merlo, A., et al., 5'' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med, 1995. 1(7): p. 686-92.
36. Nakamura, H., et al., Antagonism between apoptotic (Bax/Bcl-2) and anti-apoptotic (IAP) signals in human osteoblastic cells under vector-averaged gravity condition. Ann N Y Acad Sci, 2003. 1010: p. 143-7.
37. Park, J.C., et al., Protective effect of Oenanthe javanica on the hepatic lipid peroxidation in bromobenzene-treated rats and its bioactive component. Planta Med, 1996. 62(6): p. 488-90.
38. Quentin, T., et al., Altered mRNA expression of the Rb and p16 tumor suppressor genes and of CDK4 in transitional cell carcinomas of the urinary bladder associated with tumor progression. Anticancer Res, 2004. 24(2B): p. 1011-23
39. Richards, R.J., Networks controlling pneumocyte proliferation. Modulation of oncogene and tumor suppressor gene expression in a hamster model of chronic lung injury with varying degrees of pulmonary neuroendocrine cell hyperplasia. Hum Exp Toxicol, 1994. 13(12): p. 909-10.
40. Scambia, G., et al., Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors. Br J Cancer, 1994. 69(6): p. 995-9.
41. Sawada, N., et al., Expression of p21(waf-1/cip-1) is significantly induced in the livers of LEC rats with chronic liver injury. Jpn J Cancer Res, 1996. 87(11): p. 1102-5.
42. Weinberg, R.A., The retinoblastoma protein and cell cycle control. Cell, 1995. 81(3): p. 323-30.
43. Wittmann, S., et al., Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis. Cancer Res, 2003. 63(1): p. 93-9.
44. Xiong, Y., et al., p21 is a universal inhibitor of cyclin kinases. Nature, 1993. 366(6456): p. 701-4.
45. Yoshida, K., I. Murohashi, and K. Hirashima, p53-independent induction of p21 (WAF1/CIP1) during differentiation of HL-60 cells by tumor necrosis factor alpha. Int J Hematol, 1996. 65(1): p. 41-8.
46. Zhang, H.S., A.A. Postigo, and D.C. Dean, Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell, 1999. 97(1): p. 53-61.
47. Zhang, Y., N. Fujita, and T. Tsuruo, Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene, 1999. 18(5): p. 1131-8.
48. Zhang, Y., N. Fujita, and T. Tsuruo, p21Waf1/Cip1 acts in synergy with bcl-2 to confer multidrug resistance in a camptothecin-selected human lung-cancer cell line. Int J Cancer, 1999. 83(6): p. 790-7.
49. 行政院衛生署統計資料:Department of Health,Executive Yuan,Taiwan,R.O.C Cancer registry Annual report for Taiwan area,2007
50. Clinical Application of Flow Cytometry :Immunophenotyping of Leukemic Cells ; Approved Guideline , NCCLS Vol 18 No. 8 1998 June 9, 37-45.
51. 希望之路--面對膀胱癌. 中華民國癌症希望協會
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top