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 was a monomeric 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.