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首页> 外文期刊>Leukemia and lymphoma >Quercetin suppresses the proliferation of multiple myeloma cells by down-regulating IQ motif-containing GTPase activating protein 1 expression and extracellular signal-regulated kinase activation
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Quercetin suppresses the proliferation of multiple myeloma cells by down-regulating IQ motif-containing GTPase activating protein 1 expression and extracellular signal-regulated kinase activation

机译:槲皮素通过下调含IQ基序的GTPase活化蛋白1表达和细胞外信号调节的激酶活化来抑制多发性骨髓瘤细胞的增殖

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摘要

The flavonoid quercetin has shown anti-tumor effects against a variety of solid tumors. However, its effects on multiple myeloma (MM) remain unclear. In this study we examined the proliferation of human myeloma cell lines U266, KM3 and RPMI8226 and MM derived cells from four patients with MM after quercetin treatment, and detected the expression of IQ motif-containing GTPase activating protein 1 (IQGAP1), a scaffold protein involved in mitogen-activated protein kinase (MAPK) signaling, by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that quercetin inhibited the proliferation of MM cells in a dose-and time-dependent manner, accompanied by reduced IQGAP1 expression at mRNA and protein levels, and reduced extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Furthermore, we found that quercetin inhibited the interaction between IQGAP1 and ERK1/2 in RPMI8226 cells. In summary, our results suggest that quercetin suppresses the proliferation of MM cells by down-regulating IQGAP1 expression and ERK activation, and has potential as a novel agent to target oncogenic kinase cascades for MM therapy.
机译:类黄酮槲皮素对多种实体瘤表现出抗肿瘤作用。然而,其对多发性骨髓瘤(MM)的影响仍不清楚。在这项研究中,我们检查了槲皮素治疗后四名患有MM的人骨髓瘤细胞系U266,KM3和RPMI8226和MM衍生细胞的增殖,并检测了含有IQ模体的GTPase活化蛋白1(IQGAP1)的表达。通过逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹分析,参与有丝分裂原激活的蛋白激酶(MAPK)信号传导。我们发现槲皮素以剂量和时间依赖性的方式抑制MM细胞的增殖,并伴随着mRNA和蛋白质水平的IQGAP1表达降低,以及细胞外信号调节激酶1/2(ERK1 / 2)活化降低。此外,我们发现槲皮素抑制RPMI8226细胞中IQGAP1和ERK1 / 2之间的相互作用。总而言之,我们的结果表明槲皮素通过下调IQGAP1表达和ERK激活来抑制MM细胞的增殖,并且有潜力作为靶向MM疗法的致癌激酶级联的新型药物。

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