Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression.

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.