在体外低剂量的博特佐米布会诱导亡并独立降低多发性骨髓瘤中氨酸S转移酶和氨酸过氧化酶的活性,考虑到GSTT1和GSTM1基因变异
Szymon Zmorzynski1, Sylwia Popek-Marciniec1, Beata Biernacka2
1Laboratory of Genetics, Academy of Zamosc, 22-400 Zamosc, Poland.
Genes
|March 28, 2024
概括
在多发性骨髓瘤细胞中,博特佐米布治疗会改变谷氨酶活性,在某些药物度下,特定的基因变异 (GSTT1,GSTM1) 会影响这些变化.
科学领域:
- 在瘤学瘤学.
- 药物基因组学 药物基因组学
- 生物化学 生物化学
背景情况:
- 多发性骨髓瘤 (MM) 是血细胞的癌症.
- 博尔特佐米布是MM的关键治疗剂.
- 谷氨 (GSH) 及其相关酶在细胞保护和药物代谢中发挥作用.
研究的目的:
- 研究博特佐米布对MM细胞中谷氨水平和酶活性的影响.
- 分析GSTT1和GSTM1基因变异与这些生化变化之间的关联.
主要方法:
- 在MM患者和健康捐赠者中使用多重PCR对GSTT1和GSTM1基因进行基因定型.
- 在体外治疗MM骨髓细胞,使用不同度的博特佐米布 (1-4nM).
- 通过光显微镜和ELISA评估亡,GSH度和谷氨酶活性 (GST,GPx).
主要成果:
- 博尔特佐米布诱导了亡,并降低了GST和谷氨过氧化酶 (GPx) 的活性.
- 在GSTT1-null和GSTT1-present基因型之间观察到GSTT1活动的显著差异,在1和2nM bortezomib.
- 在GSTM1-null和GSTM1-present基因型之间,GST活性在4nM的博特佐米布之间也存在差异.
结论:
- 博尔特佐米布会影响GST和GPx酶的活性.
- GST活动与GSTT1和GSTM1基因变异有关,特别是在特定的博特佐米布度下.
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