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二十二碳六烯酸(DHA)和 JQ1 联合抑制结直肠癌细胞生长。

Synergistic antitumor activity of DHA and JQ1 in colorectal carcinoma.

机构信息

Institute of Marine Biology& Pharmacology, Ocean College, Zhejiang University, Zhoushan, Zhejiang, 316021, China.

Institute of Marine Biology& Pharmacology, Ocean College, Zhejiang University, Zhoushan, Zhejiang, 316021, China.

出版信息

Eur J Pharmacol. 2020 Oct 15;885:173500. doi: 10.1016/j.ejphar.2020.173500. Epub 2020 Aug 27.

Abstract

Colon cancer is still a major disease plaguing humans. In this study, we evaluated the synergistic antitumor effects of the combination of BRD4 inhibitor JQ1 and docosahexaenoic acid (DHA) in colon cancer. We demonstrated that simultaneous exposure to JQ1 and DHA resulted in strong synergistic antiproliferative and proapoptotic effects related to inhibition of expression of c-Myc and activation of NF-κB in colon cancer cell lines. At the same time, the synergetic anticancer effect had been confirmed in vivo. For in vivo experiments, JQ1 and DHA resulted in more significant tumor growth inhibition (53.7%) in a human colon cancer HCT116 xenograft model, comparing with the moderate inhibition in JQ1-treated (31.9%) or DHA-treated groups (20.3%). Because DHA is the predominant component of fish oil, our data suggest that this nontoxic dietary supplement could be administered with BRD4 inhibitor during therapy for CRC, which lay an important foundation for the development of therapeutic regimens for CRC.

摘要

结肠癌仍然是困扰人类的主要疾病。在这项研究中,我们评估了 BRD4 抑制剂 JQ1 和二十二碳六烯酸(DHA)联合应用在结肠癌中的协同抗肿瘤作用。我们证明,JQ1 和 DHA 同时暴露导致结肠癌细胞系中 c-Myc 表达抑制和 NF-κB 激活相关的强烈协同抗增殖和促凋亡作用。同时,体内实验也证实了协同抗癌作用。对于体内实验,JQ1 和 DHA 在人结肠癌 HCT116 异种移植模型中导致更显著的肿瘤生长抑制(53.7%),与 JQ1 治疗组(31.9%)或 DHA 治疗组(20.3%)的中度抑制相比。因为 DHA 是鱼油的主要成分,我们的数据表明,这种无毒的膳食补充剂可以在 CRC 的治疗中与 BRD4 抑制剂一起使用,为 CRC 的治疗方案的发展奠定了重要基础。

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