Interleukin 23 promotes hepatocellular carcinoma metastasis via NF-kappa B induced matrix metalloproteinase 9...

Hepatocellular carcinoma (HCC) is one of the most popular cancers in the world with poor prognosis, which often develops from chronic liver inflammatory diseases. Interleukin 23 (IL-23) is an inflammatory cytokine which is reported to play an important role in tumor development in animal model. While the function of IL-23 in HCC development remains unknown, so we investigate the role of IL-23 in HCC progression in this study.

Transcript level of IL-23, interleukin17A (IL-17A) and matrix metalloproteinases 9 (MMP9) in clinical HCC samples (n=81) was determined by qPCR. Protein expression pattern of IL-23 in primary and metastatic HCC tissues pairs (n=49 pairs) was determined by immunohistochemistry staining. Cell migration, invasion, RNA interfering and immune blotting were used to characterize the functional and signaling mechanisms in IL-23-treated HCC. Compared with paired non-tumor tissue, higher IL-23 expression was detected in HCC tumor tissues with metastasis. Immunohistochemistry staining confirmed the high expression of IL-23 in metastasis HCC. Immune blotting demonstrated that IL-23 was highly expressed in HCC cell lines with metastasis. Functional study found that IL-23 could promote HCC cell migration and invasion. Molecular analysis revealed that IL-23 could upregulate MMP9 expression via NF-κB/p65 signaling activation and IL-17A could improve IL-23 expression in tumor cells directly via activating NF-κB/p65 signaling pathway.

IL-23 could promote HCC metastasis by the upregulation of MMP9 expression via activating NF-κB/p65 signaling pathway. At the same time, IL-17A could further promote IL-23 expression in HCC tumor cells.