期刊文献+

c-FLIP反义寡核苷酸对食管癌EC109细胞裸鼠移植瘤抑制作用的实验研究 被引量:2

Inhibitory effect of c-FLIP-ASODN on transplantation tumors of the esophagus cancer cell line EC109 in nude mice:an experimental study
在线阅读 下载PDF
导出
摘要 目的研究细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白反义寡核苷酸(c-FLIP-ASODN)对食管癌EC109细胞裸鼠移植瘤的作用。方法采用食管癌EC109细胞株建立裸鼠移植瘤模型,将其分为空白对照组、脂质体转染组、无义寡核苷酸(SODN)组、ASODN组。通过移植瘤生长曲线、终末瘤重,免疫组化法检测c-FLIP蛋白表达、增殖指数,RT-PCR检测移植瘤c-FLIPmRNA变化,TUNEL检测凋亡指数,观察c-FLIP-ASODN对食管癌裸鼠移植瘤的作用。结果ASODN组治疗后移植瘤生长缓慢,实验结束时ASODN组瘤重及瘤体积明显低于其它各组,抑瘤率为68.19%。ASODN组移植瘤组织c-FLIPmRNA及蛋白、Ki-67抗原表达较其它各组明显减少,而移植瘤细胞凋亡指数明显高于其它各组(P均<0.01)。其余三组上述指标间比较差异无统计学意义(P>0.05)。结论c-FLIP-ASODN对食管癌EC109细胞裸鼠移植瘤生长有抑制作用,其机制与降低的c-FLIPmRNA和蛋白表达、抑制移植瘤细胞的增殖活性及促进肿瘤细胞凋亡有关。 Objective To explore the inhibitory effect of cellular Fas-associated death domain-like IL-1 beta converting enzyme inhibitory protein (c-FLIP) antisense oligodeoxynucleotides (ASODN) on transplantation tumor of the esophagus cancer cell line EC109 in nude mice. Methods Nude mice bearing EC109 cancer cells were established and divided into the control group, the liposome group, the sense oligonucleotide(SODN) group and the ASODN group. A transplantation tumor growth curve was drawn, and the inhibition ratio was calculated according to the tumor weight. The immunohistochemistry SP method was used to determine the expression of c-FLIP and Ki-67 antigen of the transplantation tumors. RT-PCR was used to determine the expression of c-FLIP mRNA. Terminal deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) was used to determine the apoptosis of the transplantation tumors. Results The transplantation tumors of the ASODN group slowly grew after taking drugs. The tumor volume and the tumor weight of the ASODN group were decreased compared with those of the other control groups. The tumor inhibitory rate was 68.19%. The expressions of c-FLIP mRNA and protein, and the Ki-67 antigen of the ASODN group were lower than those of other control groups. The apoptosis of the transplantation tumors of the ASODN group was higher than that of the other control groups. There were statistically significant differences between the ASODN group and the other groups( P 〈 0.05), but no statistically significant differences were found among the control group, the liposome group and the SODN group( P 〉 0.05). Conclusion c-FLIP ASODN has an anticancer activity on the esophagus cancer cell line EC109 in vivo, which is related to its role in decreasing the expressions of c-FLIP mRNA and protein, inhibiting the growth of the transplantation tumors and inducing the apoptosis of cancer ceils.
出处 《山东大学学报(医学版)》 CAS 北大核心 2007年第12期1234-1238,共5页 Journal of Shandong University:Health Sciences
关键词 食管肿瘤 寡脱氧核苷酸类 反义 细胞凋亡 基因 c-FLIP 裸鼠 Esophagus cancer Antisense oligodeoxynucleotides Apoptosis Gene therapy, c-FLIP Nude mice
  • 相关文献

参考文献12

  • 1Kim Y, Suh N, Spore M, et al. An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL- induced apoptosis [ J ]. J Biol hem, 2002, 277 ( 25 ) : 22320- 22329.
  • 2Heeje K, Katharine A W, Robert W G Ⅲ, et al. Human CD34^+ hematopoietic stem/progenitor cells express high levels of FLIP and are resistant to fas-mediated apoptosis[J]. Stem Cells, 2002, 20(2) : 174-182.
  • 3Bullani R R, Huard B, Viard L I, et al. Selective expression of FLIP in malignant melanocytic skin lesions [ J ]. J Invest Dermatol, 2001, 117(2): 360-364.
  • 4Irisarri M, Plumas J, Bonnefoix T, et al. Resistance to CD95 mediated apoptosis through constitutive cFLIP expression in a non-Hodgkin's lymphoma B cell line[J]. Leukemia, 2000, 14(12) :2149-2158.
  • 5Ryu B K, Lee M G, Chi S G, et al. Increased expression of cFLIP-L in colonic adenoc-arcinoma[J]. J Pathol, 2001, 194(1) : 15-19.
  • 6Trauzold A, Schmiedel S, Roder C, et al. Multiple and synergistic deregu- lations of apoptosis-controlling genes in pancreatic carcinoma cells [ J ]. Br J Cancer, 2003, 89 (9):1714-1721.
  • 7Osaki M, Kase S, Adachi K, et al. Inhibition of the PI3K- Akt signaling pathway enhances the sensitivity of Fas-mediated apoptosis in human gastric carcinoma cell line, MKN-45 [J]. J Cancer Res CAin Oncol, 2004, 130(1):8-14.
  • 8Qi H, Ohh M. The von Hippel-Lindau tumor suppressor protein sensitizes renal cell carcinoma cells to tumor necrosis factor-induced cytotoxicity by suppressing the nuclear factor-kappaB-dependent antiapoptotic pathway [ J ]. Cancer Res, 2003, 63(21) :7076-7080.
  • 9Simone F, Eric M, Klaus M D, et al. Metabohc Inhibitors Sensitize for CD95 (APO-1/Fas) induced apoptosis by down- regulating Fas-associated death domain-like interleukin-1 converting enzyme inhibitory protein expression [ J ]. Cancer Res, 2000, 60(14):3947-3956.
  • 10Zhang X D, Franco A, Myers K, et al. Relation of TNF-related apoptosis-inducing hgand (TRAIL) receptor and FLICE- inhibitory protein expression to TRAIL-induced apoptosis of melanoma[J]. Cancer Res, 1999, 59(11):2747-2753.

同被引文献23

  • 1Xiao-DongZhou,Jie-PingYu,Hong-XiaChen,Hong-GangYu,He-ShengLuo.Expression of cellular FLICE-inhibitory protein and its association with p53 mutation in colon cancer[J].World Journal of Gastroenterology,2005,11(16):2482-2485. 被引量:7
  • 2刘志能,唐良萏.cFLIP与人类疾病[J].重庆医学,2006,35(1):78-81. 被引量:2
  • 3石景森.胆囊癌确定治疗的思维程序[J].中华肝胆外科杂志,2006,12(3):157-158. 被引量:18
  • 4顾宇平,束永前.非小细胞肺癌组织中cFLIP和P53蛋白的表达[J].中国现代医学杂志,2006,16(21):3254-3256. 被引量:6
  • 5Irmler M,Thome M, Hahne M, et al. Inhibition of death receptor signals by eelluar FLIP[J]. Nature,1997,388(6638) :190 -195.
  • 6Krueger A, Baumann S, Krammer PH, et al. FLICE-inhibitory proteins : regulators of death receptor - mediated apoptosis [ J ]. Mol Cell Biol, 2001,21 (24) : 8247 - 8254.
  • 7Ryu BK,Lee MG,Chi SG,ct al. Increased expression of cFLIP(L) in colonic adcnocarcinoma[ J]. J Pathol,2001,194 ( 1 ) : 15 - 19.
  • 8Medema JP,de Jong J,van Hall T,et al. Immune escape of tumors in vivo by expression of celluar FLlCE-inhibitory protein[J]. J Exp Med, 1999,190(7 ) : 1033 - 1038.
  • 9Perlman H, Pagliari KI, Georganas C ,et al, FLICE-inhibitory protein expression during macrophage differentiation confers resistance to fas -mediated apoptosis[J]. J Exp Med, 1999,190 ( 11 ) : 1679 - 1688.
  • 10Ahn JH, Park SM, Cho HS ,et al. Non-apoptotic signaling pathways activated soluble Fas ligand in serum-starved human fsibroblasts. Mitogeactivated protein kinases and NF-κB-dependent gene expression. [ J]. J Biol Chem,2001,276(50) :47100-47106.

引证文献2

二级引证文献3

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部