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恶性淋巴瘤细胞对TRAIL诱导凋亡的抵抗及其分子机制

Mechanism of TRAIL-induced Apoptotic Resistance in Lymphoma Cells
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摘要 目的：探讨在体外恶性淋巴瘤细胞对TRAIL（TNF—related apoptosis—inducing ligand）诱导凋亡的抵抗作用及其分子机制。方法：TRAIL处理恶性淋巴瘤U937细胞后，在不同的时间采用MTT法检测药物对细胞的毒性作用；流式细胞术检测细胞周期；Western—blot法检测Bax蛋白质水平变化；实时荧光定量RT—PCR法检测BaxmRNA的表达情况。结果：TRAIL的浓度在500μg／L时可抑制U937的细胞生存，但其抑制率低于正常对照细胞Hmy2．ciR；TRAIL阻滞U937细胞周期于G0／G，期；但这种阻滞效应较Hmy2．ciR细胞明显减弱。Western—blot法检测TRAIL处理的U937细胞Bax蛋白表达水平下降；实时荧光定量RT—PCR法检测BaxmRNA的表达水平却未见差异性改变。结论：TRAIL在诱导恶性淋巴瘤细胞凋亡过程中出现抵抗，这种作用可能与促凋亡蛋白Bax表达水平下降有关。Bax蛋白表达水平的下降可能是由于翻译后修饰导致Bax蛋白降解。 Objective： To investigate the mechanism of TRAIL-induced apoptotic resistance in lymphoma cells. Methods： U937 cells were treated with TRAIL in vitro and the cell growth index was evaluated by MTT assay. The cell cycle was detected by flow cytometry. The levels of Bax protein and mRNA were measured by Western blot and real time RT-PCR, respectively. Results： TRAIL inhibited survival of U937 cells at a concentration of 500 μg/L, but the inhibition rate was lower than that in the control cells （Hmy2.ciR）. TRAIL arrested U937cells in G0/G1 phases, but this effect was significantly weaker when compared to that in the control cells. Further studies showed that the Bax protein level was decreased in TRAIL-treated U937 cells but no change was found in Bax mRNA expression. Conclusion： U937 cells are resistant to TRAIL-induced apopto- sis. This effect may be related to a decrease in Bax protein which may be caused by degradation of Bax at the post-translational level in TRAIL-treated U937 cells.
作者 赵天锁 史玉荣 任贺 郝继辉
机构地区 天津市肿瘤防治重点实验室
出处 《中国肿瘤临床》 CAS CSCD 北大核心 2009年第3期156-158,162,共4页 Chinese Journal of Clinical Oncology
基金 国家自然科学基金资助(编号:30600754)
关键词 TRAIL 淋巴瘤细胞 凋亡抵抗 TRAIL Lymphoma cells Apoptotic resistance
分类号 R733.1 [医药卫生—肿瘤]
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参考文献10

  • 1Wiley SR, Schooley K, Smolak PJ, et al. Identification and characterization of a new member of the TNF family that induces apoptosis[J]. Immunity, 1995, 3(6): 673-682.
  • 2Bossen C, Ingold K, Tardivel A, et al. Interactions of tumor necrosis factor(TNF) and TNF receptor family members in the mouse and human[J]. J Biol Chem, 2006, 281(20): 13964-13971.
  • 3Hao JH, Yu M, Liu FT, et al. Bcl-2 inhibitors sensitize rumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by uncoupling of mitochondrial respiration in human leukemic CEM cells[J]. Cancer Res, 2004, 64(10): 3607-3616.
  • 4佟海侠,张锦华,陆春伟,张继红.IFNγ对TRAIL诱导神经母细胞瘤细胞凋亡的调节作用[J].中国肿瘤临床,2005,32(23):1321-1324. 被引量：6
  • 5Song JH, Bellail A, Tse MC, et al. Human astrocytes are resistant to Fas ligand and rumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis[J].J Neurosci, 2006, 26(12):3299-3308.
  • 6Liu FT, Agrawal SG, Gribben JG, et al. Bortezomib blocks Bax degradation in malignant B cells during treatment with TRAIL[J]. Blood, 2008, 111(5): 2797-2805.
  • 7Li B, Dou Q P. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression[J]. Proc Natl Acad Sci U S A, 2000, 97(8): 3850-3855.
  • 8Fecker LF, Geilen CC, Tchernev G, et al. Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis[J]. J Invest Dermatol, 2006, 126(6): 1366-1371.
  • 9Hao XS, HaoJH, Liu FT, et al. Potential mechanisms of leukemia cell resistance to TRAIL-induced apoptosis[J]. Apoptosis, 2003, 8(6): 601-607.
  • 10郝继辉,俞鸣,贾丽,柳凤亭,李强,郝希山.蛋白酶体抑制剂在TRAIL诱导恶性淋巴瘤细胞凋亡中的协同作用[J].中国肿瘤临床,2007,34(3):129-131. 被引量：1

二级参考文献21

  • 1佟海侠,张锦华,陆春伟,张继红.IFNγ对TRAIL诱导神经母细胞瘤细胞凋亡的调节作用[J].中国肿瘤临床,2005,32(23):1321-1324. 被引量：6
  • 2郝继辉,俞鸣,贾丽,柳凤亭,郝希山.BH3结构域拟似物BH3I-2'诱导人白血病细胞凋亡机理的探讨[J].中国肿瘤临床,2005,32(23):1367-1370. 被引量：2
  • 3Griffith 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.
  • 4Eggert 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.
  • 5Johnsen 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.
  • 6Liu 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.
  • 7Nimmanapalli 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.
  • 8Nosel 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.
  • 9Yang 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.
  • 10Muhlethaler-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.

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中国肿瘤临床
2009年 第3期

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