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RACK1对硼替佐米诱导的多发性骨髓瘤细胞凋亡及MAPK/ERK通路的影响
引用本文:卢燕华,涂先吾,彭红华,李国平,廖良书.RACK1对硼替佐米诱导的多发性骨髓瘤细胞凋亡及MAPK/ERK通路的影响[J].现代生物医学进展,2019,19(24):4637-4641.
作者姓名:卢燕华  涂先吾  彭红华  李国平  廖良书
作者单位:岳阳职业技术学院 湖南 岳阳 414000;岳阳市第一人民医院骨科 湖南 岳阳 414000;中南大学湘雅三医院肿瘤内科 湖南 长沙410000
基金项目:国家自然科学基金项目(81176306)
摘    要:目的:探讨蛋白激酶C受体(Receptor for activated C kinase1,RACK1)对硼替佐米(Bortezomi,Bor)诱导的多发性骨髓瘤(Multiple myeloma,MM)细胞凋亡及MAPK/ERK通路的影响。方法:选取6例岳阳市第一人民医院收治的MM患者及6名正常体检者,用实时荧光定量PCR检测血浆及人MM细胞系中RACK1 m RNA的表达。将MM细胞分为3组:对照组(不干预)、Bor组(75n M的Bor干预12 h)和Bor+siRACK1组(RACK1 si RNA转染24 h后再行Bor干预)。CCK-8法检测各组细胞中的细胞存活率,Hoechest 33342染色检测细胞凋亡,Western Blot检测MAPK/ERK通路相关蛋白表达。结果:与正常体检者相比,MM患者血浆及MM细胞系中RACK1 m RNA表达显著增加(P0.05)。Bor作用12 h、24 h和48 h可显著降低MM细胞的存活率(P0.05)。与对照组相比,Bor组和Bor+siRACK1组细胞存活率显著降低,Bor+siRACK1组细胞存活率明显高于Bor组(P0.05)。Hoechest 33342染色显示对照组细胞核染色均一,未见凋亡小体,Bor组见少量凋亡小体,而Bor+siRACK1组细胞见大量凋亡小体,表现为核固缩或碎块状;与对照组相比,Bor组和Bor+siRACK1组细胞中多发性骨髓瘤细胞凋亡率显著增加(P0.05),Bor+siRACK1组多发性骨髓瘤细胞凋亡率明显高于Bor组(P0.05)。三组间多发性骨髓瘤细胞凋亡率对比差异有统计学意义(P0.05)。与对照组相比,Bor组和Bor+siRACK1组细胞中p-P38和p-ERK的表达显著降低,而Bor+siRACK1组p-P38和p-ERK的表达低于Bor组(P0.05),3组间P38和ERK的表达对比差异无统计学意义(P0.05)。结论:RACK1沉默可增强Bor诱导的MM细胞凋亡及生长抑制,其机制可能与MAPK/ERK途径抑制有关。

关 键 词:蛋白激酶C受体  硼替佐米  多发性骨髓瘤细胞  凋亡  MAPK/ERK通路
收稿时间:2019/8/6 0:00:00
修稿时间:2019/8/28 0:00:00

Effect of RACK1 on Bortezomib-induced Apoptosis and MAPK/ERK Pathway in the Multiple Myeloma Cells
LU Yan-hu,TU Xian-wu,PENG Hong-hu,LI Guo-ping,LIAO Liang-shu.Effect of RACK1 on Bortezomib-induced Apoptosis and MAPK/ERK Pathway in the Multiple Myeloma Cells[J].Progress in Modern Biomedicine,2019,19(24):4637-4641.
Authors:LU Yan-hu  TU Xian-wu  PENG Hong-hu  LI Guo-ping  LIAO Liang-shu
Institution:Yueyang vocational and technical college, Yueyang, Hunan, 414000, China;Department of orthopedics, the First People''s Hospital of Yueyang, Yueyang, Hunan, 414000, China;Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410000, China
Abstract:ABSTRACT Objective: To investigate the effect of RACK1 on Bordzomib (Bor) induced apoptosis and MAPK/ERK pathway in multiple myeloma (MM) cells. Methods: 6 cases of MM patients admitted to the First People''s Hospital of Yueyang and 6 normal subjects were selected. Real-time quantitative PCR was used to detect the expression of RACK1 mRNA in the plasma and human MM cell lines. MM cells were divided into 3 groups: control group (no intervention), Bor group (75 nM Bor intervention for 12 h) and Bor+siRACK1 group (RACK1 siRNA transfection for 24 h followed by Bor intervention). The cell viability of each group were detected by CCK-8 method, the apoptosis was detected by Hoechest 33342 staining, and the expressions of MAPK/ERK pathway-related proteins were detected by Western Blot. Results: Compared with normal subjects, RACK1 mRNA expression was significantly increased in the plasma of MM patients and human MM cell lines(P<0.05). Bor significantly reduced the viability of MM cells at 12 h, 24 h and 48 h (P<0.05). Compared with the control group, the viability in the Bor group and the Bor+siRACK1 group were significantly lower than that of the Bor group (P<0.05). Hoechest 33342 staining showed that the control group had uniform nuclear staining, and no apoptotic bodies was found, while a small number of apoptotic bodies were found in the Bor group, a large number of apoptotic bodies were observed in the Bor+siRACK1 group, which showed nuclear pyknosis or fragmentation. Compared with the control group, the apoptotic rate of MM cells in the Bor group and the Bor+siRACK1 group were significantly increased (P<0.05), and the apoptotic rate of MM cells in the Bor+siRACK1 group was significantly higher than that in the Bor group (P<0.05). Compared with the control group, the expressions of p-P38 and p-ERK were significantly decreased in the Bor group and the Bor+siRACK1 group, and the expression of p-P38 and p-ERK in the Bor+siRACK1 group was lower than the Bor group (P<0.05). There were no significant difference in the expressions of P38 and ERK among the 3 groups (P>0.05). Conclusion: RACK1 silencing enhances Bor-induced apoptosis and growth inhibition of MM cells, and its mechanism may be related to the inhibition of MAPK/ERK pathway.
Keywords:RACK1  Bortezomib  Multiple Myeloma Cells  Apoptosis  MAPK/ERK Pathway
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