Induction of apoptosis in hematological cancer cells by dorsomorphin correlates with BAD upregulation
Induction of apoptosis in hematological cancer cells by dorsomorphin correlates with BAD upregulation
复制标题
Dorsomorphin 诱导血液癌细胞凋亡与 BAD 上调相关。
DOI：
10.1016/j.bbrc.2019.11.157
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发表时间：
2020-02-12
影响因子：
3.1
通讯作者：
Wan, Xiaochun
中科院分区：
文献类型：
--
作者：
Liu, Zhao;Zhang, Guizhong;Wan, Xiaochun
AMPK通常是一种肿瘤抑制因子。然而，一旦癌症发生，AMPK反而成为肿瘤促进剂，推动癌症的发展。对于这种AMPK驱动的癌症，阻断AMPK可能是一种有价值的治疗策略。在这里，我们显示AMPK在各种血液病肿瘤中表达上调，并在维持肿瘤细胞的活性方面发挥关键作用。多索吗啡阻断AMPK信号通路可显著诱导Jurkat、K562细胞系及原发肿瘤B细胞的凋亡。在机制上，多索吗啡显著上调Bad的表达，Bad是参与启动细胞凋亡的Bcl-2基因家族中的一个促凋亡成员。通过RNA干扰减少BAD表达可阻止AMPK抑制引起的细胞凋亡。因此，我们的数据发现BAD整合了多索吗啡的促凋亡作用，并为AMPK促进血液肿瘤细胞生存信号的机制提供了新的见解。(C)2019 Elsevier Inc.保留所有权利。
AMPK is generally a tumor suppressor. However, once cancer arises, AMPK becomes a tumor promoter instead, driving cancer development. For such AMPK-driven cancers, AMPK blockade may be a valuable therapeutic strategy. Here we show that AMPK is upregulated in a variety of hematological cancers and plays key roles in maintaining viability of tumor cells. Blockade of AMPK signaling by dorsomorphin markedly induces apoptosis in Jurkat, K562 cell lines as well as primary cancerous B cells. Mechanistically, dorsomorphin significantly upregulates the expression of BAD, a pro-apoptotic member of the Bcl-2 gene family involved in initiating apoptosis. Reduction of BAD expression by RNA interference prevents apoptosis in response to AMPK inhibition. Thus, our data found BAD integrates the pro-apoptotic effects of dorsomorphin and provided novel insights into the mechanisms by which AMPK facilitates survival signaling in hematologic tumor cells. (C) 2019 Elsevier Inc. All rights reserved.