具有不同P53功能的两种多发性骨髓瘤细胞系中的基因表达
Gene Expression in Two Multiple Myeloma Cell Lines With Different P53 Functionality.
作者信息
Drozdkova Denisa Hrckova, Gursky Jan, Minarik Jiri, Überall Ivo, Kolar Zdenek, Trtkova Katerina Smesny
机构信息
Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
出版信息
Anticancer Res. 2020 Sep;40(9):4979-4987. doi: 10.21873/anticanres.14501.
BACKGROUND/AIM: Multiple myeloma is a highly heterogeneous disease of clonal plasma cells. Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their precise mechanisms of actions are not well understood.
MATERIALS AND METHODS
Cell-cycle regulation and pro-apoptotic effects of two histone deacetylase inhibitors, suberohydroxamic acid (SAHA) and suberoylanilide hydroxamic acid (SBHA), were analyzed in multiple myeloma cell lines RPMI8226 and U266 with differing TP53 status using gene-expression analysis.
RESULTS
Enhanced expression of cyclin-dependent kinase inhibitor 1A (CDKN1A/p21) detected in the TP53-deleted U266 cell line after SAHA treatment indicates the P53-independent mode of transcriptional activation of CDKN1A gene. In contrast, CDKN1A gene expression was significantly increased by both SBHA and SAHA treatment of TP53-mutated RPMI8226 cells.
CONCLUSION
SAHA appears to be a potentially effective pro-apoptotic and anticancer drug with universal application in the treatment of heterogeneous populations of multiple myeloma cells.
背景/目的：多发性骨髓瘤是一种克隆性浆细胞高度异质性疾病。组蛋白去乙酰化酶（HDAC）抑制剂是有前景的抗癌药物，但其确切作用机制尚不完全清楚。
材料与方法
使用基因表达分析，在具有不同TP53状态的多发性骨髓瘤细胞系RPMI8226和U266中分析两种组蛋白去乙酰化酶抑制剂，辛二酰羟肟酸（SAHA）和辛二酰苯胺羟肟酸（SBHA）的细胞周期调控和促凋亡作用。
结果
SAHA处理后，在TP53缺失的U266细胞系中检测到细胞周期蛋白依赖性激酶抑制剂1A（CDKN1A/p21）表达增强，表明CDKN1A基因的转录激活模式不依赖于P53。相比之下，SBHA和SAHA处理TP53突变的RPMI8226细胞均显著增加了CDKN1A基因表达。
结论
SAHA似乎是一种潜在有效的促凋亡抗癌药物，可普遍应用于治疗异质性多发性骨髓瘤细胞群体。
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