Investigating Anti-Tumor Effects of Irisin in Cervical Cancer Cells: Cell Viability, Migration, and Tumor-Associated Macrophage Polarization
Cervical cancer is a major concern in women's health. Investigating the biological behavior of cancer cells can help to understand the underlying pathogenesis and offer novel insights into disease management. Therefore, this study evaluated the effect of irisin on the biological behaviors of cervical cancer cells and elucidated its underlying mechanism. Cell viability of Caski and HeLa cells under different irisin concentrations was examined using the cell counting kit-8 (CCK-8) assay. Cell proliferation and autophagy levels were assessed at protein and mRNA levels using Western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analyses, respectively. Apoptosis was determined by assessing the levels of activated caspase-3, caspase-8, and caspase-9 using corresponding enzyme-linked immunosorbent assay (ELISA) kits. The impact of irisin on cell cycle and apoptosis rates was evaluated using flow cytometry analysis. However, the migratory capability of irisin-treated cells was assessed using the scratch healing assay. Furthermore, expression levels of matrix metalloproteinases (MMP2, MMP7, and MMP9) were determined using WB analysis, and the Transwell assay assessed the invasive potential of the cells. The impact of irisin on macrophage polarization was examined through CD86 and CD206 typing using flow cytometry, and macrophage polarization status was determined by detecting the levels of inflammatory cytokines (interleukin (IL)-6, IL-10) and tumor necrosis factor-α (TNF-α). Then, THP-1 cells were directly co-cultured with cervical cancer cells to detect their effect on their biological behavior with or without irisin treatment, aiming to explore the underlying mechanism. Irisin reduces cervical cancer cell viability and decreases the protein and mRNA expression levels of minichromosome maintenance complex component 2 (MCM2), antigen identified by monoclonal antibody Ki67 (Ki67), and proliferating cell nuclear antigen (PCNA) ( Irisin exhibits potent anti-cancer effects on cervical cancer cells by modulating several key cellular processes and altering the tumor microenvironment. Irisin effectively inhibits the proliferation, invasion, and migration of cervical cancer cells and affects the levels of autophagy and apoptosis. Furthermore, it inhibits cancer cells by affecting the polarization of tumor-associated macrophages, underscoring their potential as a novel therapeutic target for treating cervical cancer.