FoxO1, a Potential Therapeutic Target, Regulates Mitochondrial Dysfunction and Pyroptosis in LPS-Induced Human Cervical Cancer Cells

Background: Chronic inflammation plays an important role in the development of cervical cancer. Studies have demonstrated that transcription factors forkhead box protein O1 (FoxO1) have been reported to play important roles in various cancers. Aim: The purpose of this study was to investigate the effect of FoxO1 gene on lipopolysaccharide (LPS)-induced inflammation and intracellular pyroptosis in the development and progression of human cervical cancer cells (SiHa). Methods: : In this study, FoxO1 expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. SiHa cells migration and proliferation was detected using the transwell assay and 3 H‑TdR assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation and changes in the mitochondrial membrane potential (ΔΨm). Results: : Our study demonstrated that LPS inhibited FoxO1 gene expression, and the silence of FoxO1 gene caused the accumulation of ROS, decreases in the ΔΨm and mitochondrial morphology change). However, either overexpression of FoxO1 or metformin could reverse the LPS-induced mitochondrial dysfunction, cell pyroptosis, migration and proliferation. Conclusions: : Our study indicated that FoxO1 as a potential therapeutic target to cure against LPS-induced human cervical cancer in a mitochondria-dependent manner.