Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression.
Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression.
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Mmethylprednisolone 抑制慢性淋巴细胞白血病细胞系 MEC-1 中受 LEF-1 表达调节的 Wnt 信号通路。
DOI：
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Wang, Xin
中科院分区：
文献类型：
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作者：
Liu, Yan-Xia;Zhang, Feng;Yuan, Ting;Wang, Xin
高剂量甲基泼尼松龙 (HDMP) 一直是复发性慢性淋巴细胞白血病 (CLL) 患者的有效挽救疗法，但人们对糖皮质激素诱导的细胞死亡的确切机制知之甚少。为了探索糖皮质激素诱导的细胞死亡的机制，我们研究了 HDMP 对经典 Wnt 信号传导的影响，该信号传导是 CLL 发病机制中的关键途径。在这项研究中，人类 CLL 细胞系 MEC-1 与不同浓度的甲基强的松龙一起孵育。 CCK8法检测细胞增殖活性，TUNEL法评价细胞凋亡效果。 Western blot检测活性caspase 3和Wnt信号通路关键蛋白（LEF-1、β-catenin）。 RT-PCR 评估 β-catenin、LEF-1、c-myc 和 cyclin D1 的 mRNA 水平。我们观察到高浓度的甲泼尼龙可以抑制MEC-1细胞的增殖活性，促进活性Caspase 3的相对表达，并诱导细胞凋亡。此外，甲泼尼龙可抑制LEF-1蛋白表达，从而下调c-myc和cyclin D1 mRNA水平，但不影响β-catenin和LEF-1 mRNA转录水平。本研究结果表明，甲基泼尼松龙可以通过下调LEF-1蛋白表达来抑制Wnt信号通路，为HDMP治疗CLL提供了新的机制。
High dose methylprednisolone (HDMP) has been an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia (CLL), while little is known about the exact mechanisms implicated in glucocorticoid-induced cell death. To explore the mechanism of glucocorticoid-induced cell death, we investigated the effect of HDMP on canonical Wnt signaling which emerged as a key pathway implicated in the pathogenesis of CLL. In this study, the human CLL cell line MEC-1 was incubated with various concentrations of methylprednisolone. Cell proliferation activity was detected by CCK8 assay, the apoptotic effect was evaluated by TUNEL assay. Western blot was used to detect active-caspase 3, and the key proteins in Wnt signaling pathway (LEF-1, β-catenin). RT-PCR was performed to assess the mRNA levels of β-catenin, LEF-1, c-myc and cyclin D1. We observed that high concentration of methylprednisolone could suppress the proliferation activity of MEC-1 cells, promote the relative expression of active-caspase 3, and induce apoptotic cell death. Furthermore, methylprednisolone could inhibit LEF-1 protein expression, consequently down-regulate mRNA levels of c-myc and cyclin D1, but could not affect the transcription level of β-catenin and LEF-1 mRNA. The results of this study indicate that methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression, indicating a novel mechanism for HDMP therapy in CLL.
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DOI：
10.1172/jci22094
发表时间：
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期刊：
The Journal of clinical investigation
影响因子：
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作者：
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