No abstract

Quercetin is a widely distributed, bioactive flavonoid compound, which displays potential to inhibit fibrosis in several diseases. The purpose of our study was to determine the effect of quercetin treatment on renal fibrosis and investigate the mechanism. Human proximal tubular epithelial cells (HK‐2) stimulated by transforming growth factor‐β1 (TGF‐β1) and a rat model of unilateral ureter obstruction (UUO) that contributes to fibrosis were used to investigate the role and molecular mechanism of quercetin. PD153035 (N‐[3‐Bromophenyl]‐6,7‐dimethoxyquinazolin‐4‐amine) was used to inactivate EGFR (epidermal growth factor receptor). The level of fibrosis, proliferation, apoptosis, and oxidative stress in HK‐2 were measured. All data are presented as means ± standard deviation (SD). p‐value < .05 was considered statistically significant. In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK‐2 cells, quercetin significantly ameliorated the EMT induced by TGF‐β1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis.

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 3 H-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.

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 3H‑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.