HLJ2 Effectively Ameliorates Colitis-Associated Cancer via Inhibition of NF-[kappa]B and Epithelial--Mesenchymal Transition

Introduction: Colitis-associated cancer (CAC) accounts for approximately 15% of IBD patient mortalities. However, currently available anti-CAC drugs possess many disadvantages including safety, specificity and side effects. Therefore, the development of novel anti-CAC compounds is imperative. HLJ2 w...

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Bibliographic Details
Published in:Drug design, development and therapy development and therapy, 2020-10, Vol.14, p.4291
Main Authors: Song, Huachen, Tang, Xiaonan, Li, Xiang, Wang, Yufei, Deng, Anjun, Wang, Wenjie, Zhang, Haijing, Qin, Hailin, Wu, Lian Qiu
Format: Article
Language:English
Subjects:
Analysis
Cancer
Cancer prevention
Colitis
Cytokines
Gastrointestinal diseases
Health aspects
Stem cells
Transforming growth factors
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Summary:Introduction: Colitis-associated cancer (CAC) accounts for approximately 15% of IBD patient mortalities. However, currently available anti-CAC drugs possess many disadvantages including safety, specificity and side effects. Therefore, the development of novel anti-CAC compounds is imperative. HLJ2 was a monomelic compound synthesized by our institute and reported to have an effect on ulcer colitis. Methods: In vivo the AOM/DSS-induced CAC model was used to evaluate the effects of HLJ2 on ameliorating CAC symptoms, immunohistochemical analysis was used to analyze the pathological damage to colons and epithelial-mesenchymal transition was for changes of cytokines. In vitro, flow cytometric analysis, immunofluorescence and Western blot were used to detect the inhibition effect of HLJ2 on nuclear factor-[kappa]B and epithelial-mesenchymal transition in TGF-[beta]1-stimulated SW480 cells. Results: In the AOM/DSS animal model, HLJ2 was demonstrated to inhibit the secretion of inflammatory cytokines and nuclear factor-[kappa]B, levels of tumorigenesis-related proteins including snail, and finally inhibited a key step in metastasis, epithelial-mesenchymal transition. In vitro, HLJ2 was also shown to inhibit nuclear factor-[kappa]B and epithelial-mesenchymal transition in TGF-[beta]1-stimulated SW480 cells in accordance with in vivo results. Meanwhile, the nuclear factor-[kappa]B inhibitor could interrupt the effect of HLJ2 on epithelial-mesenchymal transition. Discussion: HLJ2 may ameliorate CAC through inhibiting nuclear factor-[kappa]B and then downstream epithelial-mesenchymal transition. The combination of the obvious improvement in effects on CAC without obvious side effects suggests that HLJ2 could be developed as a potential CAC therapeutic candidate. Keywords: inflammatory bowel disease, colitis-associated cancer, EMT
ISSN:1177-8881
1177-8881
DOI:10.2147/DDDT.S262806