目的:探讨三氧化二砷(ATO)治疗急性早幼粒细胞白血病(APL)与糖酵解的关系,以及其潜在的分子机制。
方法:使用GEO数据库分析APL患者RPL22L1表达的改变及其与糖酵解的相关性。在9个配对的临床样品中评估RPL22L1和糖酵解的水平。用ATO处理NB4细胞和敲低RPL22L1的NB4细胞。采用RT-PCR和Westernblot检测RPL22L1蛋白和mRNA的表达,含量是用葡萄糖测定的,丙酮酸,和乳酸检测试剂盒。最后,使用CCK8检测细胞增殖,通过划痕测定迁移,和细胞凋亡通过流式细胞术,并检测了ATO在NB4细胞中的生物学功能。
结果:GSE213742和GSE234103数据集中RPL22L1的表达在人APL细胞中表现出显著的增加,特别是NB4细胞。RPL22L1在GSE213742和GSE234103基因表达基质中显著升高,在人APL细胞NB4中,进一步分析发现RPL22L1与糖酵解呈强正相关。细胞实验表明,ATO抑制NB4细胞中的RPL22L1,抑制APL细胞中的糖酵解。ATO在抑制增殖方面发挥了关键作用,迁移,以及NH4细胞的侵袭。
结论:ATO通过抑制RPL22L1的表达调节APL的溶瘤通路,这可能有助于其治疗效果。
OBJECTIVE: To investigate the relationship between the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO) and glycolysis, as well as its underlying molecular mechanism.
METHODS: The GEO database was used to analyze alterations in the expression of RPL22L1 in APL patients and its correlation with glycolysis. The levels of RPL22L1 and glycolysis were assessed in 9 paired clinical samples. NB4 cells and NB4 cells with knockdown of RPL22L1 were treated with ATO. The protein and mRNA of RPL22L1 were detected using RT-PCR and Western blot, and the content was determined by using glucose, pyruvate, and lactate detection kits. Finally, detection of cell proliferation using CCK8, migration by scratch assay, and apoptosis by flow cytometry, and the biological function of ATO in NB4 cells was examined.
RESULTS: The expression of RPL22L1 in GSE213742 and GSE234103 datasets exhibited a significant increase in human APL cells, specifically NB4 cells. RPL22L1 in GSE213742 and GSE234103 gene expression matrix was significantly elevated in human APL cells NB4 cells, and further analysis found RPL22L1 showed a strong positive correlation with glycolysis. Cellular experiments showed that ATO inhibited RPL22L1 in NB4 cells and inhibited glycolysis in APL cells. The ATO played a pivotal role in suppressing the proliferation, migration, as well as invasion of NH4 cells.
CONCLUSIONS: ATO regulates the blycolytic pathway in APL by inhibiting RPL22L1 expression, and this may contribute to its therapeutic effects.