HLJ2 Effectively Ameliorates Colitis-Associated Cancer via Inhibition of NF-κB and Epithelial-Mesenchymal Transition

• Published in: Drug design, development and therapy Vol. 14; pp. 4291 - 4302
• Main Authors: Song, Huachen, Tang, Xiaonan, Li, Xiang, Wang, Yufei, Deng, Anjun, Wang, Wenjie, Zhang, Haijing, Qin, Hailin, Wu, LianQiu
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2020; Dove; Dove Medical Press
• Subjects: Animal models; Animals; Antibodies; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Agents, Phytogenic - toxicity; Azoxymethane; Cancer; Cell Line, Tumor; Colitis; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - complications; Colitis, Ulcerative - pathology; colitis-associated cancer; Colon - pathology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - etiology; Colonic Neoplasms - pathology; Colorectal cancer; Cytokines; Cytokines - metabolism; Dextran Sulfate; emt; Epithelial-Mesenchymal Transition - drug effects; Female; Flow cytometry; Heterocyclic Compounds, 4 or More Rings - therapeutic use; Heterocyclic Compounds, 4 or More Rings - toxicity; Humans; Immunofluorescence; In vivo methods and tests; Inflammation; Inflammatory bowel disease; Laboratory animals; Mesenchyme; Metastases; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-κB protein; Nuclear engineering; Nuclear safety; Original Research; Side effects; Spleen; Transforming Growth Factor beta1 - pharmacology; Tumor necrosis factor-TNF; Tumorigenesis; Beijing China; St Louis Missouri; United States > US; China; EMT; colitis-associated cancer; inflammatory bowel disease
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S262806

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.