BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo
BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo
复制标题
BRD4抑制剂和组蛋白脱乙酰酶抑制剂在体外和体内协同抑制胆囊癌的增殖
DOI：
10.1111/cas.14102
复制
发表时间：
2019-07-11
期刊：
影响因子：
5.7
通讯作者：
Gong, Wei
中科院分区：
文献类型：
--
作者：
Liu, Shilei;Li, Fengnan;Gong, Wei
胆囊癌（GBC）是最常见的胆管恶性肿瘤，死亡率高。在体外和体内实验中，我们证明了BRD4抑制剂JQ1和组蛋白去乙酰化酶抑制剂亚eroylanilide hydroxyamic acid （SAHA）协同抑制GBC细胞。我们的研究结果表明，JQ1和SAHA共处理可显著抑制GBC细胞的增殖、细胞活力和转移，诱导细胞凋亡和G2/M阻滞，而对良性细胞的影响较小。在体内，JQ1或SAHA治疗后，GBC异种移植模型的肿瘤体积和重量均显著降低；同时，共处理效果最强。进一步研究表明，上述抗癌作用与下调BRD4、抑制PI3K/AKT和MAPK/ERK通路有关。这些发现强调JQ1和SAHA是潜在的治疗药物，它们的联合治疗是GBC的有希望的治疗策略。
Gallbladder cancer (GBC) is the most common malignancy of the bile duct and has a high mortality rate. Here, we demonstrated that BRD4 inhibitor JQ1 and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) synergistically inhibited the GBC cells in vitro and in vivo. Our results showed that cotreatment with JQ1 and SAHA significantly inhibited proliferation, cell viability and metastasis, and induced apoptosis and G2/M arrest in GBC cells, with only minor effects in benign cells. In vivo, tumor volumes and weights of GBC xenograft models were significantly decreased after treatment with JQ1 or SAHA; meanwhile, the cotreatment showed the strongest effect. Further study indicated that the above anticancer effects was associated with the downregulation of BRD4 and suppression of PI3K/AKT and MAPK/ERK pathways. These findings highlight JQ1 and SAHA as potential therapeutic agents and their combination as a promising therapeutic strategy for GBC.