【摘要】 目的 :研究Bcl 2家族成员在 5 氟尿嘧啶 (5 FU)和CD3ε介导的T淋巴细胞凋亡中的作用 ,阐述T淋巴细胞凋亡的分子机制 ,为相关肿瘤的治疗提供依据。方法 :用CD3ε特异的单克隆抗体 (2 0 0 μg/ml)和 5 FU(2 5 μg/ml)单独或联合刺激JK、TJK和T3JK细胞 ,诱导细胞凋亡 ,用MTS比色法检测细胞死亡率 ,用Westernblot检测Bid的表达和活化。用脂质体的方法转染细胞。结果 :CD3ε特异的单克隆抗体和 5 FU分别单独处理TJK细胞 ,都能诱导其凋亡并伴随Bid的活化 ,二者联合使用能显著增加TJK细胞凋亡和Bid的活化。Bcl 2过表达可明显降低TJK细胞对 5 FU的敏感性。结论 :Bcl 2家族成员参与CD3ε和 5 FU诱导的T淋巴细胞凋亡的调节 ,Bcl 2过表达能显著抑制T淋巴细胞对 5 FU的敏感性。更多还原

【Abstract】 Objective:To investigate the regulation of Bcl 2 family on T lymphocyte apoptosis mediated by CD3ε and/or 5 FU (5 fluorouracil) and to provide a novel insight of the apoptosis signaling pathway and the implication for the clinic therapy of T lymphocyte leukemia.Methods:JK,TJK and T3JK cells stimulated with anti CD8 mAb (200 μg/ml) cross link and/or 5 FU (2 5 μg/ml) for 34 h.MTS assay was used to detect cell viability.Bcl 2 and Bid activation and expression were detcted by Western blot.Bcl 2 expression plasmid was stably transfected into TJK cells by electroporation method (250 μF,300 Volts).Results:Bid was activated in the TJK apoptosis induced by CD3ε specific monoclonal antibody or 5 FU.The apoptosis rate and Bid activation increased remarkably in the TJK cells cotreated with the CD3ε specific monoclonal antibody and 5 FU.Bcl 2 overexpression in the TJK cells decreased the sensitivity to 5 FU and maintained cell cycle.Conclusion:Bid plays an important role in the regulation of T lymphocyte apoptosis and is localized at the cross point of the two signaling pathway mediated by CD3ε and 5 FU,respectively. [更多还原