S1P4受体通过Akt调节骨髓瘤细胞凋亡的机制研究  

Mechanism of S1P4 receptor in regulating apoptosis of myeloma cells via Akt

作　　者：杨融辉[1] 石小岩[1] 傅迪[1] 仲媛[1] 郑金科[1] 廖爱军[1] 

机构地区：[1]中国医科大学附属盛京医院血液内科,沈阳110004

出　　处：《实用药物与临床》2016年第11期1328-1331,共4页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金(81272629)

摘　　要：目的探讨S1P受体对多发性骨髓瘤(MM)细胞系LP-1生存及凋亡的影响及调控机制。方法应用芬戈莫德(FTY720)抑制LP-1细胞S1P受体,CCK-8法测定细胞生存率,流式细胞仪检测凋亡率。应用qRT-PCR方法检测LP-1细胞中S1P受体的表达情况。应用S1P4R-shRNA敲除S1P4受体,采用荧光显微镜及qRT-PCR法测定病毒感染率及感染后S1P4受体表达。Western blot方法检测S1P4受体敲除后抗凋亡蛋白Akt、Survivin、Birc4、Bag-1表达情况。结果 FTY720处理后,LP-1细胞生存率明显下降,凋亡率明显上升,与对照组相比差异均具有统计学意义(P<0.05)。LP-1细胞中S1P4受体呈高表达,敲除S1P4受体后,抗凋亡蛋白Akt、Survivin、Birc4、Bag-1表达明显下降(P<0.05)。结论 S1P受体对LP-1细胞生存具有重要作用。其中S1P4受体在LP-1细胞凋亡中起主要作用。S1P4受体可通过Akt调节下游抗凋亡蛋白Survivin、Birc4、Bag-1的表达,从而影响LP-1细胞凋亡。Objective To explore the effect of SI P receptor on the survival and apoptosis of LP-1 cell line of MM and its mechanism.Methods Fingolimod（FTY720） was used to inhibit SIP receptor of LP-1 cell line;CCK-8assay was performed to evaluate cell viability and flow cytometry was performed to detect the apoptosis rate.The expression of SIP receptors was measured by qRT-PCR.SlP4R-shRNA was used to knock down S1P4 receptor,then the expression of SI P4 was measured by fluorescence microscope and qRT-PCR assay.The expression of antiapoptotic protein Akt,Bag-l,Birc4 and Survivin in S1P4 silented cell was detected by Western blot.Results The LP-1 cell survival rate decreased significantly after FTY720 treatment,and the apoptosis rate was also significantly increased（P〈0.05）.S1P4 receptor expression in LP-1 cell line was the highest,while the expression of anti-apoptotic protein Akt,Bag-l,Birc4 and Survivin decreased obviously after the S1P4 receptor was knocked down（P〈0.05）.Conclusion SIP receptors play an important role in the survival of LP-1 cells,while S1P4 receptor plays a major role in the apoptosis of LP-1 cells.S1P4 receptor can regulate the expression of antiapoptotic protein Bag-1,Birc4 and Survivin via Akt,and affect the apoptosis of LP-1 cells

关 键 词：S1P4受体 多发性骨髓瘤 AKT 凋亡 

分 类 号：R733.3[医药卫生—肿瘤]