Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors
Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors
复制标题
抑制 SRC-3 可增强人类癌细胞对组蛋白脱乙酰酶抑制剂的敏感性
DOI：
10.1016/j.bbrc.2016.07.063
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发表时间：
2016-09-09
影响因子：
3.1
通讯作者：
Mi, Yanjun
中科院分区：
文献类型：
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作者：
Zou, Zhengzhi;Luo, Xiaoyong;Mi, Yanjun
SRC-3在多种肿瘤类型中广泛表达，参与肿瘤细胞增殖和凋亡。组蛋白去乙酰化酶（HDAC）抑制剂是一种很有前景的抗肿瘤药物。然而，HDAC抑制剂在实体瘤中的疗效较差，限制了其进一步的临床应用。在这里，我们报道了一项新的发现，即SRC-3的缺失增强了乳腺癌和肺癌细胞对HDAC抑制剂（SAHA和罗米地辛）的敏感性。相反，SRC-3的过表达减少了saha诱导的癌细胞凋亡。此外，我们发现SRC-3抑制剂蟾毒灵增加了HDAC抑制剂诱导的癌细胞凋亡。蟾毒灵和SAHA联合使用对抑制AKT活化和降低Bcl-2水平特别有效。总的来说，这些积累的数据可能会指导新的乳腺癌和肺癌治疗方法的开发。(C) 2016 Elsevier Inc.版权所有。
SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. (C) 2016 Elsevier Inc. All rights reserved.