“Regulator of G‐protein Signaling 10 (RGS10) inhibits NF‐κB signaling, COX‐2 and inflammatory cytokine production in ovarian cancer cells”

Abstract

Epithelial Ovarian Cancer (EOC) is the fifth leading cause of cancer‐related deaths among females in the United States. NF‐κB signaling and production of inflammatory mediators have been strongly linked to ovarian cancer progression and chemoresistance. Regulator of G‐protein Signaling 10 (RGS10) regulates ovarian cancer survival and chemoresistance, and has been linked to NF‐κB signaling in immune cells. The goal of the current study was to determine the ability of RGS10 to inhibit NF‐κB signaling and subsequent inflammatory effects in ovarian cancer. RGS10 is a negative regulator of Gαi signaling and multiple Gi coupled GPCRs are implicated in ovarian cancer. Therefore, we predicted that RGS10 regulates NF‐κB signaling and inflammatory cytokines downstream of Gαi mediated‐pathway. We found that knock‐down of RGS10 enhanced NF‐κB phosphorylation and produced significantly higher levels of COX‐2 and TNF‐α mRNA compared to cells transfected with control siRNA in SKOV‐3 EOC cells. Surprisingly, we found that Pertussis toxin (ptx), which is a Gαi inhibitor, had no effects on upregulation of p‐NF‐κB, COX‐2 and TNF‐α expressions‐mediated by RGS10 knock‐down. These results provide insight in the mechanism that RGS10 utilizes to regulate ovarian cancer survival and chemoresistance.Support or Funding Information National Institutes of Health Rivkin Center for Ovarian Cancer. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.