HLJ2 Effectively Ameliorates Colitis-Associated Cancer via Inhibition of NF-κB and Epithelial-Mesenchymal Transition
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 monomeric...
Saved in:
Published in | Drug design, development and therapy Vol. 14; pp. 4291 - 4302 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New Zealand
Taylor & Francis Ltd
01.01.2020
Dove Dove Medical Press |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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 monomeric compound synthesized by our institute and reported to have an effect on ulcer colitis.
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-κB and epithelial-mesenchymal transition in TGF-β1-stimulated SW480 cells.
In the AOM/DSS animal model, HLJ2 was demonstrated to inhibit the secretion of inflammatory cytokines and nuclear factor-κB, 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-κB and epithelial-mesenchymal transition in TGF-β1-stimulated SW480 cells in accordance with in vivo results. Meanwhile, the nuclear factor-κB inhibitor could interrupt the effect of HLJ2 on epithelial-mesenchymal transition.
HLJ2 may ameliorate CAC through inhibiting nuclear factor-κB 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1177-8881 1177-8881 |
DOI: | 10.2147/DDDT.S262806 |