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雷公藤内酯醇通过 microRNAs 增强多发性骨髓瘤细胞对地塞米松的敏感性。

Triptolide enhances the sensitivity of multiple myeloma cells to dexamethasone via microRNAs.

机构信息

Department of Hematology, Zhejiang University School of Medicine, Zhejiang Province, People's Republic of China.

出版信息

Leuk Lymphoma. 2012 Jun;53(6):1188-95. doi: 10.3109/10428194.2011.638069. Epub 2012 Feb 13.

Abstract

Recently triptolide (TPL) has been proved to have the capacity to inhibit the proliferation of multiple myeloma (MM) cells as well as leukemic cells in vitro. In the present study, we found a synergistic effect when TPL was added to dexamethasone to induce apoptosis in MM.1S cells. This combination induced a significantly higher proportion of apoptotic cells compared with those treated with each drug separately. TPL down-regulated the expression of miR142 - 5p and miR181a, which have been shown to inhibit glucocorticoid receptor (GR) expression. MicroRNA mimics and inhibitors inhibited or enhanced the synergistic effect between TPL and dexamethasone in inducing apoptosis in MM.1S cells, suggesting an important role of miR142 - 5p and miR181a in GR regulation by TPL. The in vitro proapoptotic effect of TPL associated with dexamethasone reveals a new lead for further clinical investigation into the treatment of patients with MM with TPL.

摘要

最近,雷公藤红素(TPL)已被证明具有抑制多发性骨髓瘤(MM)细胞和白血病细胞体外增殖的能力。在本研究中,我们发现 TPL 与地塞米松联合使用可诱导 MM.1S 细胞凋亡,具有协同作用。与单独使用每种药物相比,该联合用药诱导的凋亡细胞比例显著更高。TPL 下调了 miR142-5p 和 miR181a 的表达,已知它们可抑制糖皮质激素受体(GR)的表达。miRNA 模拟物和抑制剂抑制或增强了 TPL 和地塞米松诱导 MM.1S 细胞凋亡的协同作用,表明 miR142-5p 和 miR181a 在 TPL 调节 GR 方面发挥着重要作用。TPL 与地塞米松联合具有体外促凋亡作用,为进一步研究 TPL 治疗 MM 患者提供了新的线索。

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