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.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Qing-Min
QM
Yao
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Pei-Pei
PP
Li
Department of Gynaecology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Shu-Mei
SM
Liang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Kang
K
Lu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Xiao-Juan
XJ
Zhu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Yan-Xia
YX
Liu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Feng
F
Zhang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Ting
T
Yuan
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Xin
X
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism*; D008775:Methylprednisolone / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000187:drug effects*
D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D019938:Cyclin D1; C505407:CASP3 protein, human; D053148:Caspase 3; D008775:Methylprednisolone
LEF-1; Methylprednisolone; chronic lymphocytic leukemia; wnt signaling pathway; β-catenin