演題詳細

一般口演 / Oral Session

一般口演 91 (Oral Session 91) :AML:細胞の特性 2

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日程
2013年10月13日(日)
時間
16:00 - 17:00
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
矢野 道広 (Michihiro Yano):1
1:秋田大学医学部 小児科
 
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Knock-down of FZD1 reduced MDR1/P-gp expression in leukemic cells through the Wnt/β-catenin pathway

演題番号 : OS-3-104

王 艶華 (Yan-Hua Wang):1、今井 陽一 (Yoichi Imai):1、志関 雅幸 (Masayuki Shiseki):1、丁 曄 (Ye Ding):1、泉二 登志子 (Toshiko Motoji):1

1:Dept. Hematology, Tokyo Women's Med Univ., Japan

 

The relationship between the Wnt/β-catenin signaling pathway and acquired multidrug resistance in leukemic cells is not well known. We have previously reported that the Wnt receptor frizzled 1 (FZD1) is associated with the multidrug resistance 1 gene (MDR1). Knock-down of FZD1 by shRNA significantly decreases MDR1 and P-glycoprotein (P-gp) expression in resistant leukemic cell lines such as K562/Vin, K562/ADM, and NOMO-1/ADM. In the present study, we investigated whether drug sensitivity recovered after FZD1-silenced and P-gp expression was decreased through activation of the Wnt/β-catenin pathway. The cytotoxicity assay indicated restoration of drug sensitivity to daunorubicin, adriamycin, and vincristine in FZD1-silenced resistant cells. Western blot analysis revealed that protein levels of β-catenin and a T-cell transcription factor 4 (TCF4) in the cytoplasmic/nuclear fraction were significantly decreased in FZD1-silenced cells. In addition, treatment with shFZD1 significantly reduced cell proliferation and suppressed colony formation in these cells. Elevated p27 and decreased cyclin D1 protein levels were also observed. To the best of our knowledge, this is the first report that FZD1 silencing induced down-regulation of MDR1/P-gp and restored sensitivity to chemotherapy drugs in drug-resistant leukemic cells. Our findings suggest that FZD1 promotes the activation of β-catenin/TCF4 and increases the proliferative capacity of the cells through the regulation of cyclin D1 expression. FZD1 seems to mediate multidrug resistance through the Wnt/β-catenin signaling pathway.

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