Effects of Forkhead box O1 on lipopolysaccharide-induced mitochondrial dysfunction in human cervical squamous...

Persistent infection and chronic inflammation play important roles in the development of cervical squamous cell carcinoma. Forkhead box O1 (FOXO1) is a notable regulator of mitochondrial metabolism, which is involved in the occurrence and development of tumors. The present study explored the effects of FOXO1 in human cervical squamous carcinoma SiHa cells. The expression of FOXO1 was examined using reverse transcription-quantitative PCR, western blotting and immunohistochemical staining. SiHa cell migration and proliferation were detected using Transwell and ³H-TdR assays. Mitochondrial functions were assessed based on reactive oxygen species (ROS) generation and changes in the mitochondrial membrane potential (ΔΨm). The present study revealed that lipopolysaccharide (LPS) stimulation significantly inhibited the expression of FOXO1 in cervical squamous carcinoma SiHa cells; while silencing FOXO1 resulted in the accumulation of mitochondrial ROS, a decrease in the ΔΨm and abnormal morphology of mitochondria. Accordingly, enhancing FOXO1 expression or treatment with metformin, which protects mitochondrial function, reversed LPS-induced mitochondrial dysfunction, cell pyroptosis, migration and proliferation of cervical squamous carcinoma SiHa cells. Overall, the current study indicated that treatment with FOXO1 could potentially be used as therapeutic strategy to prevent LPS-induced cervical squamous cell carcinoma-related dysfunction in a mitochondria-dependent manner.