Inhibition of IL-8 Mitigates Migration and Invasion by Restraining MMP9 Expression in Liver Cancer
نویسندگان
1 Department of Pancreatic Diseases, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital (100 Minjiang Avenue, Kecheng District, Quzhou City, Zhejiang Province, Postal Code: 324000), China
2 Department of Pancreatic Diseases, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital (100 Minjiang Avenue, Kecheng District, Quzhou City, Zhejiang Province, Postal Code: 324000), China
3 Department of Pancreatic Diseases, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital (100 Minjiang Avenue, Kecheng District, Quzhou City, Zhejiang Province, Postal Code: 324000), China
4 Department of Pancreatic Diseases, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital (100 Minjiang Avenue, Kecheng District, Quzhou City, Zhejiang Province, Postal Code: 324000), China
5 Department of Pancreatic Diseases, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital (100 Minjiang Avenue, Kecheng District, Quzhou City, Zhejiang Province, Postal Code: 324000), China
doi
10.22034/ircmj.2025.490155.1634چکیده
Background and Objectives: Interleukin 8 (IL-8) is a major mediator involved in the development and progression of liver cancer. In this study, we assess whether IL-8 controls the expression of MMP-9 during the progression of liver cancer. Methods: The expression levels of IL-8, MMP-9, CXCR1, and CXCR2 in liver cancer cells with/without IL-8 knockdown or IL-8 treatment were determined by qRT-PCR and western blotting. Wound healing and Transwell assays were performed to assess the effects of IL-8-and IL-8/MMP-9-blocking antibodies on cell migration and invasion. The effects of GROα and CXCR2-neutralizing antibody on MMP-9 expression were also evaluated. Results: IL-8 and MMP-9, which were highly expressed in Huh-7 cells, were reduced by IL-8 knockdown. IL-8 treatment enhanced the expression levels of IL-8, MMP-9, CXCR1, and CXCR2. IL-8-neutralizing antibody inhibited liver cancer cell motility. MMP-9-neutralizing antibody counteracted IL-8 promotion of malignant characteristics. The IL-8-induced MMP-9 release was partially reversed by CXCR2-neutralizing antibody, but not CXCR1-neutralizing antibody. Furthermore, GROα-mediated MMP-9 release was counteracted by CXCR2-neutralizing antibody. Conclusion: The present study showed that IL-8 increased MMP-9, CXCR1, and CXCR2 expression and enhanced motility in Huh-7 liver cancer cells. These results suggested that IL-8 promotes liver cancer cell migration and invasion by upregulating MMP-9, primarily through the CXCR2 signaling pathway.
