Wnt5a enhances the response of CML cells to Imatinib Mesylate through JNK activation and γ-catenin inhibition

被引：11

作者：

Niu, Chang-Chun ^{[1
]}

Zhao, Chen ^{[1
,2
]}

Zhang, Xiao-Li ^{[1
]}

Pan, Jing ^{[1
]}

Zhao, Chen ^{[1
,2
]}

Wu, Wei-Ru ^{[1
]}

Li, Zhi-Qiang ^{[1
]}

Liu, Tao ^{[1
]}

Yang, Zhong ^{[1
]}

Si, Wei-Ke ^{[1
]}

机构：

[1] Third Mil Med Univ, Dept Clin Hematol, Chongqing 400038, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400038, Peoples R China

来源：

LEUKEMIA RESEARCH | 2013年 / 37卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Wnt5a; Chronic myeloid leukaemia; Imatinib Mesylate; JNK; beta-Catenin; gamma-Catenin; CHRONIC MYELOID-LEUKEMIA; JUN NH2-TERMINAL KINASE; N-TERMINAL KINASE; BETA-CATENIN; BCR-ABL; C-JUN; SURVIVIN EXPRESSION; STEM-CELLS; SIGNALING PATHWAY; MOLECULAR-BIOLOGY;

D O I：

10.1016/j.leukres.2013.07.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Imatinib Mesylate is widely used for the treatment of chronic myelogenous leukaemia (CML), and its effects on CML cells are influenced by several signalling proteins. The research is aimed at determining whether Wnt5a affects the effects of Imatinib Mesylate against BCR-ABL positive CML cells (K562 cells and KU812 cells) and which signalling proteins are involved in. The results showed that Wnt5a augmented the effects of Imatinib Mesylate on inhibiting CML cells proliferation and inducing apoptosis in vitro; Wnt5a enhanced the inhibition effect of Imatinib Mesylate on the growth of K562 cells xenograft tumour in an animal model. Furthermore, Wnt5a inhibited beta-catenin and its target gene Survivin, increased the activity of JNK and suppressed beta-catenin expression. When inhibiting the activity of JNK, the influence of Wnt5a on the effects of Imatinib Mesylate was attenuated. Moreover, JNK suppressed beta-catenin and its target gene Survivin, and enhanced the effects of Imatinib Mesylate. These results suggest that Wnt5a can enhance the efficacy of Imatinib Mesylate through JNK/beta-catenin/Survivin and gamma-catenin/beta-catenin/Survivin pathways. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1532 / 1537

页数：6

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