青蒿琥酯联合来那度胺对多发性骨髓瘤耐药细胞株的作用

发布时间：2018-01-30 23:02

本文关键词： 青蒿琥酯来那度胺骨髓瘤耐药　出处：《广东医学》2017年04期 　论文类型：期刊论文

【摘要】：目的探讨青蒿琥酯联合来那度胺对多发性骨髓瘤耐药(MM.1R)细胞株增殖的影响并分析其作用机制。方法实验设4组,空白对照组只加RPMI 1640培养液、来那度胺组加20μmol/L来那度胺、青蒿琥酯组加25μg/m L青蒿琥酯、来那度胺联合青蒿琥酯组加20μmol/L来那度胺浓度和25μg/m L青蒿琥酯浓度,终体积为200μL,分别对MM.1R细胞株处理24和48 h,MTT法检测细胞增殖;Western blot检测来那度胺联合青蒿琥酯处理24和48 h,MM.1R细胞株NF-κB P65蛋白,Bcl-2家族抗凋亡蛋白Bcl-xl、Mcl-1、p-Bad,多药耐药基因MDR1蛋白表达产物P-gp的表达水平。结果来那度胺、青蒿琥酯、来那度胺联合青蒿琥酯处理24和48 h,各组抑制率分别为15.16%、28.28%、45.98%和17.19%、34.53%、65.16%,与对照组比较差异均有统计学意义(P0.05,P0.01),来那度胺联合青蒿琥酯组抑制率高于单药处理组(P0.05),两药联合有良好的协同效应,两药联合处理48 h抑制率高于24 h,抑制效应呈时间依赖性;来那度胺联合青蒿琥酯处理24和48 h,MM.1R细胞株P-gp、NF-κB P65、Bcl-xl、Mcl-1、p-Bad表达量均低于对照组(P0.05),两药联合处理48 h,MM.1R细胞株NF-κB P65、Bcl-xl、Mcl-1、p-Bad蛋白表达量低于24 h(P0.05),表现出时间依赖性。结论青蒿琥酯、来那度胺可抑制耐药MM细胞增殖,两药联合有协同效应,时间依赖性下调NF-κB P65蛋白、Bcl-2家族抗凋亡蛋白Bcl-xl、Mcl-1、p-Bad的表达,降低P-gp表达水平可能为其逆转肿瘤细胞耐药的作用机制。
[Abstract]:Objective to investigate the effect of artesunate combined with renatamide on proliferation of multimyeloma resistant MM.1R cell line and analyze its mechanism. The blank control group was treated with RPMI 1640 medium, the control group with 20 渭 mol/L renadrine, and the artesunate group with 25 渭 g / mL artesunate. In combination with artesunate group, the concentration of renadrine and artesunate was 20 渭 mol/L and 25 渭 g / mL, and the final volume was 200 渭 L. MM.1R cell lines were treated for 24 h and 48 h, respectively. Western blot was used to detect the p65 protein of NF- 魏 B in MM.1R cell line treated with renalidomide combined with artesunate for 24 and 48 h. Expression level of Bcl-2 family anti-apoptotic protein Bcl-1mcl-1p-Bad. the expression level of P-gp protein product of multidrug resistance gene MDR1. Results Linadomide, artesunate. The inhibition rates of renadomide combined with artesunate for 24 h and 48 h were 15.16%, 28.28%, 45.98% and 17.19%, 34.53% and 65.16%, respectively. Compared with the control group, the difference was statistically significant (P 0.05 P 0.01). The inhibitory rate of linadmine combined with artesunate group was higher than that of single drug treatment group (P 0.05). There was good synergistic effect between the two drugs. The inhibition rate of 48 h was higher than that of 24 h, and the inhibitory effect was time-dependent. Renalidomide combined with artesunate was used to treat the cell line P-gpn- 魏 B P65, Bcl-xlc-1 and Mcl-1 in 24 and 48 hours of treatment of MM.1R cell line. The expression of p-Bad was lower than that of control group (P 0.05). Conclusion artesunate and renadamide can inhibit the proliferation of drug-resistant MM cells, and the two drugs have synergistic effect. It down-regulated the expression of Bcl-2 family anti-apoptotic protein Bcl-xl1mcl-1p-Bad in a time-dependent manner. The reduction of P-gp expression may be the mechanism of its reversal of drug resistance in tumor cells.
【作者单位】：广东省第二人民医院血液科;
【基金】：国家自然科学基金资助项目(编号:81400168) 广东省医学科研基金立项项目(编号:A2013128) 广东省中医药局建设中医药强省科研课题(编号:20131104) 广东省第二人民医院引进人才科研启动基金(编号:YY2014-002)
【分类号】：R733.3
【正文快照】： 虽然近10年来随着硼替佐米、来那度胺等新药以及自体造血干细胞移植的应用,目前多发性骨髓瘤(multiple myeloma,MM)患者的缓解率及生存期得到较大程度的提高,但由于骨髓瘤细胞容易产生耐药,绝大多数患者最终都会进入难治或复发阶段,MM目前仍被认为是无法治愈的疾病,如何克服肿

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