期刊文献+

IFNγ对TRAIL诱导神经母细胞瘤细胞凋亡的调节作用 被引量:6

The Effect of IFNγ on TRAIL-induced Apoptosisin Neuroblastoma Cells
下载PDF
导出
摘要 目的:探讨IFNγ(γ-干扰素)对TRAIL(肿瘤坏死因子相关凋亡诱导配体)诱导神经母细胞瘤细胞株SH-SY5Y凋亡的影响及其发生机制。方法:应用RT-PCR方法检测IFNγ作用前后SY5Y细胞Caspase8的表达;应用四甲基偶氮唑蓝(MTT)比色法及流式细胞仪(FCM)检测IFNγ、TRAIL、IFNγ+TRAIL及IFNγ+Caspase8抑制剂+TRAIL对SY5Y细胞生长及凋亡的影响;应用透射电镜对凋亡细胞进行形态学观察。结果:SY5Y细胞不表达Caspase8,IFNγ作用48h后的SY5Y细胞Caspase8表达明显增加;SY5Y细胞对TRAIL不敏感,经IFNγ诱导表达Caspase8的SY5Y细胞对TRAIL敏感,且与TRAIL浓度有关,Caspase8抑制剂可明显降低TRAIL对表达Caspase8的SY5Y细胞的杀伤作用;透射电镜可见到典型的细胞凋亡特征。结论:IFNγ可逆转SY5Y细胞对TRAIL诱导凋亡的耐受,其发生机制可能是IFNγ通过上调SY5Y细胞Caspase8表达而实现的。 Objective: To study the effect of IFNγ/on TRAIL-induced apoptosis in neuroblastoma cells and its possible molecular mechanisms. Methods: The expression of Caspase 8 mRNA was detected by RT-PCR. The effects of IFNγ TRAIL, IFNγ+TRAIL and IFNγ+Caspase 8 inhibitor + TRAIL on the growth and the apoptosis of SH-SY5Y cells was detected using MTT and FCM. The morphous of the apoptosis cells was detected using the transmission electron microscope (TEM). Results: Expression of Caspase 8 was not detected in SY5Y cells but an increased expression of Caspase 8 was found after treatment with IFNγ. SY5Y cells were not sensitive to TRAIL, but IFNγ-treated SY5Y cells were sensitive to TRAIL and it was correlated with the concentration of TRAIL; the killing effect of TRAIL on Caspase 8-expressing SY5Y cells was diminished by Caspase 8 inhibitor; Typical features of apoptosis were seen by TEM. Conclusion: IFNγ can sensitize SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up regulated expression of Caspase 8.
出处 《中国肿瘤临床》 CAS CSCD 北大核心 2005年第23期1321-1324,共4页 Chinese Journal of Clinical Oncology
基金 国家自然科学基金(编号:39470739) 卫生部科学研究基金(编号:20122167) 辽宁省博士启动自然科学基金(编号:20041047) 辽宁省教育厅科研基金资助(编号:202013121)
关键词 神经母细胞瘤 凋亡 CASPASE 8 TRAIL 干扰素-Γ Neuroblastoma Apoptosis Caspase8 TRAIL IFNγ
  • 相关文献

参考文献11

  • 1Griffith TS, Anderson RD, Davidson BL, et al. Adenoviral-mediated transfer of the TNF-related apoptosis-inducing ligand/Apo2 ligand gene induces tumor cell apoptosis [J]. J Immunol, 2000,165(5):2886-2894.
  • 2Eggert A, Grotzer MA, Zuzak TJ, et al. Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression[J]. Cancer Res, 2001, 61(4):1314-1319.
  • 3Johnsen J, Pettersen I, Ponthan F, et al. Synergistic induction of apoptosis in neuroblastoma cells using a combination of Cytostatic drugs with Interfern--γand TRAIL [J]. Int J Oncol, 2004, 25 (6):1849 - 1857.
  • 4Liu W, Bodle E, Chen JY, et al. Tumor necrosis factor-related apoptosis-inducing ligand and chemotherapy cooperate to induce apoptosis in mesothelioma cell lines[J]. AmJ Respir Cell Mol Biol,2001, 25(1):111-118.
  • 5Nimmanapalli R, Perkins CL, Orlando M, et al. Pretreatment with paclitaxel enhances apo-2 ligand/tumour necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels [J].Cancer Res, 2001, 61(2):759-763.
  • 6Nosel MM, Pieters R, Voute PA, et al. The N-myc paradox: Nmyc overexpression in neuroblastoma is associated with sensitivity as well as resistance to apoptosis [J]. Cancer Lett, 2003, 197(1-2):165-172.
  • 7Yang X, Merchant MS, Romero ME, et al. Induction of caspase 8by interferon gamma renders some neuroblastoma cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB [J]. Cancer Res, 2003, 63 (5):1122-1129.
  • 8Muhlethaler-Mottet A, Balmas K, Auderset K, et al. Restoration of TRAIL-induced apoptosis in a caspase-8-deficient neuroblastoma cell line by stable re-expression of caspase-8 [J]. Ann N Y Acad Sci, 2003, 1010:195-199.
  • 9Fulda S, Debatin KM. IFN gamma sensitizes for apoptosis by upregulating caspase-8 expression through the Statl pathway [J].Oncogene, 2002, 21(15): 2295-2308.
  • 10Ebinger M, Senf L, Wachowski O, et al. Promoter Methylation Pattern of Caspase-8, P16INK4A, MGMT, TIMP-3, and ECadherin in Medulloblastoma [J]. Pathol Oncol Res, 2004, 10(1):17-21.

同被引文献53

引证文献6

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