S100A8 Mediates Autophagy and Apoptosis in Ovarian Cancer Cells via the PI3K/Akt Pathway

Background: Ovarian cancer (OC) is one of the most lethal forms of gynecological malignancies. Previous studies indicate that S100 calcium-binding protein A8 (S100A8) regulation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway has been implicated in the development and progression of a variety of cancers, but its effects and mechanisms in OC cells remain unclear. This study aims to explore the effect of S100A8 on autophagy and apoptosis in OC cells and the regulatory effects of the PI3K/Akt signaling pathway. Methods: Viability of OC cells was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was determined using the Transwell assay. The effect of S100A8 on autophagy in OC cells was assessed using immunofluorescence and transmission electron microscopy. Flow cytometry analysis was conducted to assess apoptosis. To study the expression of genes associated with cell viability, migration, autophagy, apoptosis, and the PI3K/Akt signaling pathway, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were performed. Results: High concentrations of S100A8 protein significantly inhibited the activity of OC cells, with the most pronounced effect observed at 72 hours (p < 0.05). S100A8 protein inhibited the proliferation of OC cells and decreased the expression level of migration-driving factors (p < 0.05). S100A8 protein promoted apoptosis and inhibited the protein levels of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II) in OC cells (p < 0.05). However, the PI3K/Akt activator blocked the inhibitory effects of S100A8 on OC cell activity, autophagy, and migration, and hindered it from promoting apoptosis. Conclusions: With its ability to inhibit proliferation, migration, and autophagy, and promote apoptosis in OC cells by inhibiting the PI3K/Akt pathway, S100A8 holds promise as a potential target for the prevention and treatment of OC, providing an effective therapeutic strategy for the clinic.