体外低硼替佐米剂量诱导多发性骨髓瘤细胞凋亡，并独立降低谷胱甘肽 S-转移酶和谷胱甘肽过氧化物酶的活性，同时考虑和基因变异。

In Vitro Low-Bortezomib Doses Induce Apoptosis and Independently Decrease the Activities of Glutathione S-Transferase and Glutathione Peroxidase in Multiple Myeloma, Taking into Account the and Gene Variants.

机构信息

Laboratory of Genetics, Academy of Zamosc, 22-400 Zamosc, Poland.

Institute of Nursing and Obstetrics, Academy of Zamosc, 22-400 Zamosc, Poland.

出版信息

Genes (Basel). 2024 Mar 21;15(3):387. doi: 10.3390/genes15030387.

DOI:10.3390/genes15030387

PMID:38540446

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10970692/

Abstract

BACKGROUND

Multiple myeloma (MM) is a malignancy derived from plasma cells. Bortezomib affects the concentration of reduced glutathione (GSH) and the activity of glutathione enzymes. The aim of our study was to analyze deletion (null/present) variants of and genes and their association with the levels of glutathione and its enzymes in bortezomib-treated cell cultures derived from MM patients.

MATERIALS AND METHODS

This study included 180 individuals (80 MM patients and 100 healthy blood donors) who were genotyped via multiplex PCR (for the / genes). Under in vitro conditions, MM bone marrow cells were treated with bortezomib (1-4 nM) to determine apoptosis (via fluorescence microscopy), GSH concentration, and activity of glutathione enzymes (via ELISA).

RESULTS

Bortezomib increased the number of apoptotic cells and decreased the activity of S-glutathione transferase (GST) and glutathione peroxidase (GPx). We found significant differences in GST activity between 1 nM (-null vs. -present), 2 nM (-null vs. -present), and 4 nM (-null vs. -present) bortezomib: 0.07 vs. 0.12, = 0.02; 0.06 vs. 0.10, = 0.02; and 0.03 vs. 0.08, = 0.01, respectively.

CONCLUSIONS

Bortezomib affects the activities of GST and GPx. GST activity was associated with and variants but only at some bortezomib doses.

摘要

背景

多发性骨髓瘤（MM）是一种源自浆细胞的恶性肿瘤。硼替佐米会影响还原型谷胱甘肽（GSH）的浓度和谷胱甘肽酶的活性。我们研究的目的是分析硼替佐米治疗的 MM 患者骨髓细胞培养物中和基因缺失（null/present）变体及其与谷胱甘肽及其酶水平的关系。

材料和方法

本研究纳入了 180 名个体（80 名 MM 患者和 100 名健康献血者），通过多重 PCR（针对和基因）进行基因分型。在体外条件下，用硼替佐米（1-4 nM）处理 MM 骨髓细胞，通过荧光显微镜观察细胞凋亡，通过 ELISA 检测 GSH 浓度和谷胱甘肽酶的活性。

结果

硼替佐米增加了凋亡细胞的数量，并降低了 S-谷胱甘肽转移酶（GST）和谷胱甘肽过氧化物酶（GPx）的活性。我们发现，在 1 nM（-null 与 -present）、2 nM（-null 与 -present）和 4 nM（-null 与 -present）硼替佐米处理时，GST 活性存在显著差异：0.07 与 0.12， = 0.02；0.06 与 0.10， = 0.02；0.03 与 0.08， = 0.01。