A novel small molecular STAT3 inhibitor, 5Br-6b, induces apoptosis and inhibits migration in colorectal cancer cells

Signal transducers and activators of transcription 3 (STAT3) represent a transcription factor that is constitutively activated in various cancers. Numerous studies have shown that STAT3 plays crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. In this study, we investigated a novel inhibitor, called -6b, to target STAT3 in colorectal cancer cells. The influence of 5Br-6b on the proliferation of colorectal cell lines SW480 and HCT116 was evaluated using an 3-(4, 5-dimethylthiazolyl)-2 and 5-diphenyltetrazolium bromide assay. We detected cell apoptosis after the treatment of 5Br-6b by flow cytometry. In addition, 5Br-6b caused the cleavage of caspase-3 and decreased the expression of Bcl-2. Cancer cell invasion and migration were measured by transwell and wound-healing assay. The potential mechanism was evaluated by western blotting and immunofluorescence. The results show that 5Br-6b inhibits the activation of STAT3, and decreases the expression of its target genes that regulate cell proliferation, migration, and apoptosis. Thus, 5Br-6b is a promising therapeutic drug candidate for colorectal cancer by inhibiting persistent STAT3 signaling. Correspondence to Maode Lai, PhD, Department of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, People's Republic of China Tel/fax: +86 25 86185555; e-mail: lmd@cpu.edu.cn Received October 9, 2017 Accepted January 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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