环孢素A抑制亲环素A对多发性骨髓瘤细胞增殖的影响

发布时间：2018-03-17 13:26

本文选题：多发性骨髓瘤　切入点：亲环素A　出处：《中国肿瘤临床》2017年04期 　论文类型：期刊论文

【摘要】：目的:亲环素A(cyclophilin A,CyPA)在多种肿瘤组织中高表达,在肿瘤形成发展中扮演重要的角色。本研究对CyPA在多发性骨髓瘤(multiple myeloma,MM)患者骨髓标本中的表达及其对MM细胞增殖、凋亡能力的影响进行研究,探讨其与MM发生、进展的相关性。方法:采用ELISA法检测骨髓标本及细胞培养上清中CyPA水平。不同浓度环孢素A(cyclosporin A,CsA)刺激MM细胞,CCK-8法检测细胞增殖能力、Western blot法检测PARP蛋白裂解评价细胞凋亡水平。结果:单克隆免疫球蛋白血症、冒烟型骨髓瘤、MM患者骨髓中CyPA浓度逐渐升高,至MM达最高值,患者治疗后CyPA浓度明显下降。CsA处理MM细胞后,CyPA分泌减少,随时间延长细胞增殖能力呈浓度依赖性逐渐减弱,PARP蛋白裂解增加、细胞凋亡增多。结论:随MM恶性程度增加,骨髓中CyPA浓度显著升高,经治疗缓解后CyPA浓度显著下降,CyPA介导的细胞增殖在MM致癌机制中可能起关键作用。CsA作为CyPA作用的抑制剂,具有促进细胞凋亡、阻碍细胞增殖的作用,无免疫抑制作用的CsA衍生物可能是潜在的MM有效治疗手段。
[Abstract]:Objective: cyclophilin Acyclophilin Acyclopa is highly expressed in various tumor tissues and plays an important role in tumor formation and development. In this study, we studied the expression of CyPA in bone marrow of patients with multiple myeloma and its effect on the proliferation of MM cells. The effect of apoptosis was studied, and the relationship between apoptosis and MM was studied. Methods: ELISA method was used to detect the level of CyPA in bone marrow and supernatant of cell culture. Cyclosporin A at different concentrations was used to stimulate MM cells. CCK-8 method was used to detect the proliferation ability of MM cells. Western blot assay was used to detect PARP protein cleavage to evaluate the cells. Level of apoptosis. Results: monoclonal immunoglobulinemia, The concentration of CyPA in the bone marrow of patients with smoking myeloma increased gradually to the highest value of MM. After treatment, the concentration of CyPA decreased significantly. The secretion of CyPA in MM cells decreased after treatment with CSA. The proliferative ability of the cells decreased in a concentration-dependent manner, and the cell apoptosis increased. Conclusion: with the increase of MM malignancy, the concentration of CyPA in bone marrow increases significantly. After treatment, the concentration of CyPA decreased significantly. CyPA-mediated cell proliferation may play a key role in the carcinogenesis of MM. CSA, as an inhibitor of CyPA, can promote cell apoptosis and hinder cell proliferation. Non-immunosuppressive CsA derivatives may be a potential effective therapy for MM.
【作者单位】：天津医科大学肿瘤医院放射治疗科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心;美国梅奥诊所血液科;
【基金】：天津医科大学肿瘤医院引进人才与博士启动基金项目(编号:B1512)资助~~
【分类号】：R733.3

【相似文献】