A Small β-Carboline Derivative "B-9-3" Modulates TGF-β Signaling Pathway Causing Tumor Regression in Vivo.

ABSTRACT: Targeting tumor microenvironment (TME) is crucial in order to overcome the anti-cancer therapy resistance. In this study, we report the antitumor activity of a newly synthesized β-carboline derivative "B-9-3." Here, this small molecule showed a promising antitumor activity in vivo along with an enhanced immune response as reflected by a reduction of regulatory T cells and increased CD4+/CD8+ T cells. Further, B-9-3 decreased the number of myofibroblasts not only in the tumor but also in the lung suggesting an anti-metastatic action. The reduction of myofibroblasts was associated with lower expression of epithelial-to-mesenchymal transition markers and a decrease of phosphorylated SMAD2/3 complex indicating the implication of TGF-β signaling pathway in B-9-3's effect. The blockade of

SUBMITTER: Zhong H 

PROVIDER: S-EPMC6063040 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature