Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway

Abstract

The aim of the present study was to explore the effect of silencing wild-type p53-induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase-3, caspase-3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl-2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated (p)-p38 MAPK. Reverse transcription-quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl-2 and caspase-3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p-p38 MAPK expression, as well as increased cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. No significant differences were observed in apoptosis and apoptosis-related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future.

Gentisyl Alcohol Inhibits Proliferation and Induces Apoptosis via Mitochondrial Dysfunction and Regulation of MAPK and PI3K/AKT Pathways in Epithelial Ovarian Cancer Cells

“…GSK3β, which usually displays upregulation by inhibition of AKT in ovarian cancer, and the S6 protein, generally known to occur downstream to PI3K/AKT, did not show significant changes with gentisyl alcohol in both ES2 and OV90 cells. The stimulation of Ras/MAPK signaling induces caspase activity, depolarized mitochondrial membranes, and reactive oxygen species (ROS) production, leading to apoptosis in ovarian cancer [27,28]. According to previous results, gentisyl alcohol induced p-P38 protein in both the ES2 and OV90 cells, similar to our results pertaining to the p-ERK1/2 activity.…”

Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways

“…On the basis of a previous study, LPS induces apoptosis of macrophages by inducing the secretion of TNFα [57]. In addition, activation or inactivation of the MAPK pathway regulates the cell apoptosis process [58]. In this study, the protective effect of EP on LPS-induced apoptosis of IPEC-J2 cells was examined by fluorescence microscopy (Figure 9).…”

Mesna ameliorates acute lung injury induced by intestinal ischemia–reperfusion in rats

“…growth factors and cellular stress 49 . The p38 MAPK signaling pathway stimulates apoptosis by phosphorylation of the key regulator p53 50 . Our findings were in consistence with the results of other researchers 51 , 52 .…”