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AD5-10与表阿霉素联合作用治疗类风湿性关节炎 被引量:2
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作者 周剑锁 史娟 +4 位作者 朱洁卿 袁海芹 刘彦信 尤欣 郑德先 《中国医学科学院学报》 CAS CSCD 北大核心 2011年第4期367-370,共4页
目的研究抗死亡受体抗体(AD5-10)与表阿霉素联合作用治疗类风湿性关节炎的机制。方法采用MTT法检测成纤维样滑膜细胞(FLS)存活率,用蛋白免疫印迹研究细胞凋亡信号通路蛋白和p53、p21的变化。结果不同剂量的表阿霉素可增强FLS对AD5-10的... 目的研究抗死亡受体抗体(AD5-10)与表阿霉素联合作用治疗类风湿性关节炎的机制。方法采用MTT法检测成纤维样滑膜细胞(FLS)存活率,用蛋白免疫印迹研究细胞凋亡信号通路蛋白和p53、p21的变化。结果不同剂量的表阿霉素可增强FLS对AD5-10的敏感性,促进FLS凋亡。表阿霉素处理可使FLS细胞中caspase-3、-8、-9,c-FLIP,Bcl-2,p53和p21表达水平发生变化。结论表阿霉素可能通过改变p53、p21、c-FLIP和Bcl-2协同AD5-10诱导FLS凋亡。 展开更多
关键词 类风湿性关节炎 成纤维样滑膜细胞 ad5-10 表阿霉素
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An agonistic monoclonal antibody against DR5 induces ROS production, sustained JNK activation and Endo G release in Jurkat leukemia cells 被引量:2
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作者 Caifeng Chen Yanxin Liul Dexian Zheng 《Cell Research》 SCIE CAS CSCD 2009年第8期984-995,共12页
We have previously reported that AD5-10, a novel agonistic monoclonal antibody against DRS, possessed a strong cytotoxic activity in various tumor cells, via induction of caspase-dependent and -independent signaling p... We have previously reported that AD5-10, a novel agonistic monoclonal antibody against DRS, possessed a strong cytotoxic activity in various tumor cells, via induction of caspase-dependent and -independent signaling pathways. The present study further demonstrates that reactive oxygen species (ROS) were generated in abundance in Jurkat leukemia cells upon AD5-10 stimulation and that ROS accumulation subsequently evoked sustained activation of c-Jun N-terminal kinase (JNK), loss of mitochondrial membrane potential, and release of endonuclease G (Endo G) from mitochondria into the cytosol. The reducing agent, N-acetylcysteine (NAC), effectively inhibited the sustained activation of JNK, release of Endo G, and cell death in Jurkat cells treated by AD5-10. Moreover, a dominant-negative form of JNK (but not of p38) enhanced NF-κB activation, suppressed caspase-8 recruitment in death-inducing signaling complexes (DISCs), and reduced adverse effects on mitochondria, thereby inhibiting AD5-10-induced cell death in Jnrkat leukemia cells. These data provide novel information on the DR5-mediated ceil death-signaling path- way and may shed new light on effective strategies for leukemia and solid tumor therapies. 展开更多
关键词 ad5-10 ROS .INK DR5 TRAIL
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