NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the mitochondria in breast cancer.
NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the mitochondria in breast cancer.
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NDRG2 通过乳腺癌线粒体中的 Bad/p53 复合物促进阿霉素敏感性
DOI：
10.18632/oncotarget.16035
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发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Wei Y;Yu S;Zhang Y;Zhang Y;Zhao H;Xiao Z;Yao L;Chen S;Zhang J
化疗耐药是乳腺癌治疗的一大难题。我们之前的研究表明，N-Myc下游调控基因2 （NDRG2）参与了p53介导的化疗诱导的细胞凋亡，其机制迄今尚不清楚。在这里，我们探讨了NDRG2在化疗耐药中的作用，重点是阿霉素（ADR），发现NDRG2表达在ADR耐药的乳腺癌细胞中下降。有趣的是，NDRG2可以通过p53依赖的方式抑制增殖、增强细胞损伤反应和促进细胞凋亡来促进ADR敏感性。我们还发现NDRG2可以通过增加其半衰期来上调Bad的表达，这与p53对线粒体的影响有关。因此，我们的集体数据提供了第一个证据，证明NDRG2促进乳腺癌敏感性依赖于p53，通过阻止p53进入细胞核而不是改变其表达。
Chemo-resistance presents a difficult challenge for the treatment of breast cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in p53-mediated apoptosis induced by chemotherapy, through a mechanism that has so far remained obscure. Here, we explored the role of NDRG2 in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2 expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2 can promote ADR sensitivity by inhibiting proliferation, enhancing cellular damage responses, and promoting apoptosis in a p53-dependent manner. We also found that NDRG2 could upregulate Bad expression by increasing its half-life, which is associated with p53 to mitochondria. Hence, our collective data provided the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent on p53 by preventing p53 from entering the nucleus rather than changing its expression.