Growth inhibition of imatinib-resistant CML cells with the T315 mutation and hypoxia-adaptation by AV65 。Va novel Wnt/υ-catenin signaling inhibitor
Growth inhibition of imatinib-resistant CML cells with the T315 mutation and hypoxia-adaptation by AV65 。Va novel Wnt/υ-catenin signaling inhibitor
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AV65 对 T315 突变和缺氧适应的伊马替尼耐药 CML 细胞的生长抑制。
DOI：
10.1016/j.canlet.2011.08.002
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
--
作者：
Nagao;R.;Ashihara;E.;Kimura;S.;Strovel;J. W.;Yao;H.;Takeuchi;M.;Tanaka;R.;Hayashi;Y.;Hirai;H.;Padia;J.;Strand;K.
我们研究了一种新的Wnt/β-catenin信号传导抑制剂AV 65对甲磺酸伊马替尼（IM）敏感和耐药的人慢性粒细胞白血病（CML）细胞的作用。AV 65抑制多种CML细胞系的增殖，包括携带T315 I突变的细胞。AV 65可降低CML细胞中β-catenin的表达，诱导细胞凋亡。此外，AV 65抑制过表达β-catenin的低氧适应原始CML细胞的增殖。AV 65与IM联合应用对CML细胞增殖具有协同抑制作用。这些结果表明，AV 65可能是一种新的治疗药物，用于治疗慢性粒细胞白血病。
We investigated the effect of a novel Wnt/β-catenin signaling inhibitor, AV65 on imatinib mesylate (IM)-sensitive and -resistant human chronic myeloid leukemia (CML) cells in vitro. AV65 inhibited the proliferation of various CML cell lines including T315I mutation-harboring cells. AV65 reduced the expression of β-catenin in CML cells, resulting in the induction of apoptosis. Moreover, AV65 inhibited the proliferation of hypoxia-adapted primitive CML cells that overexpress β-catenin. The combination of AV65 with IM had a synergistic inhibitory effect on the proliferation of CML cells. These findings suggest that AV65 could be a novel therapeutic agent for the treatment of CML.