AUTHOR=Zhao Xi , Qi Xiaoqiang , Lian Wenrui , Tong Xin , Wang Hua , Su Liya , Wei Ping , Zhuang Zhuochen , Gong Jianhua , Bai Liping 

TITLE=Trichomicin Suppresses Colorectal Cancer via Comprehensive Regulation of IL-6 and TNFα in Tumor Cells, TAMs, and CAFs

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00386

DOI=10.3389/fphar.2020.00386

ISSN=1663-9812

ABSTRACT=Trichomicin, a novel small-molecule compound isolated from fungi, has been identified with bioactivity of antitumor. In this study, a colon cancer subcutaneous mice model was used to evaluate its antitumor effect in vivo. Treatment with Trichomicin significantly inhibited the tumor growth within the xenograft mouse colon cancer model. The underlying molecular mechanism has also been investigated through the quantification of relevant proteins. The expression level of IL-6 and TNFα were reduced in tumor tissue treated with Trichomicin, consistent with results from in vitro experiments that Trichomicin suppressed the expression of IL-6 and TNFα in both tumor and stroma cells. The TNFα-dependent NF-κB and basal Stat3 signaling pathway were inhibited by Trichomicin in in vitro cell models, resulting in the reduction of immune checkpoint ligand protein PD-L1 expression in both tumor and stroma cells. Conclusively, Trichomicin, a promising new drug candidate with antitumor-activity, has been demonstrated to exert its antitumor effect against colon cancer through the inhibition of IL-6 and TNFα signaling pathway.