| 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].,2019,19(24):4637-4641 |
| 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 |
| Effect of RACK1 on Bortezomib-induced Apoptosis and MAPK/ERK Pathway in the Multiple Myeloma Cells |
| 投稿时间：2019-08-06 修订日期：2019-08-28 |
| DOI：10.13241/j.cnki.pmb.2019.24.008 |
| 中文关键词: 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 |
| 英文关键词: RACK1 Bortezomib Multiple Myeloma Cells Apoptosis MAPK/ERK Pathway |
| 基金项目:国家自然科学基金项目(81176306) |
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| 中文摘要: |
| 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 mRNA的表达。将MM细胞分为3组：对照组(不干预)、Bor组(75 nM的Bor干预12 h)和Bor+siRACK1组(RACK1 siRNA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 mRNA表达显著增加(P<0.05)。Bor作用12 h、24 h 和48 h可显著降低MM细胞的存活率(P<0.05)。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(P<0.05)。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(P<0.05)，Bor+siRACK1组多发性骨髓瘤细胞凋亡率明显高于Bor组(P<0.05)。三组间多发性骨髓瘤细胞凋亡率对比差异有统计学意义(P<0.05)。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(P<0.05)，3组间P38和ERK的表达对比差异无统计学意义(P>0.05)。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。 |
| 英文摘要: |
| 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. |
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