Interleukin-1β Inhibits Ovarian Cancer Cell Proliferation and Metastasis Through the MAPK/MMP12 Pathway

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Epithelial ovarian cancer (EOC) has a high mortality rate, with poor survival for advanced stages.
• The link between inflammation and cancer is established but not fully understood.
• Novel diagnostic and therapeutic strategies for EOC are critically needed.

Purpose of the Study:

• To investigate the role of interleukin-1β (IL-1β) in epithelial ovarian cancer (EOC) progression.
• To elucidate the molecular mechanisms underlying IL-1β's effects on EOC cells.
• To explore potential therapeutic targets related to inflammation in EOC.

Main Methods:

• Analysis of IL-1β expression in ovarian cancer tissue microarrays (TMAs).
• In vitro experiments using A2780 and SKOV3 ovarian cancer cell lines with recombinant IL-1β protein and IL-1β overexpression/deficiency.
• Transcriptome sequencing to identify downstream targets of IL-1β.
• Investigation of the MAPK/AP-1/MMP12 signaling pathway.

Main Results:

• Increased IL-1β expression was observed in ovarian cancer tissues.
• IL-1β inhibited the viability, proliferation, and metastasis of EOC cells (A2780 and SKOV3).
• IL-1β deficiency led to increased proliferation and metastasis.
• Transcriptome sequencing revealed IL-1β downregulates matrix metalloproteinase 12 (MMP12) expression.
• The MAPK/AP-1/MMP12 pathway mediates IL-1β's effects on EOC progression.

Conclusions:

• The proinflammatory cytokine IL-1β exhibits inhibitory effects on ovarian cancer cell viability and metastasis.
• IL-1β plays a protective role against EOC progression by downregulating MMP12 via the MAPK/AP-1 pathway.
• These findings enhance understanding of inflammation's role in cancer and suggest IL-1β as a potential therapeutic target for EOC.