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Therapeutic Methods and Therapies TCIM
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Eur J Pharmacol ; 885: 173500, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32861663

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Azepines/therapeutic use , Colorectal Neoplasms/drug therapy , Docosahexaenoic Acids/therapeutic use , Triazoles/therapeutic use , Animals , Apoptosis/drug effects , Cell Cycle Proteins/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , NF-kappa B/drug effects , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Transcription Factors/antagonists & inhibitors , Xenograft Model Antitumor Assays
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