Exendin‐4 exhibits a tumour suppressor effect in SKOVR‐3 and OVACR‐3 ovarian cancer cells lines by the activation of SIRT1 and inhibition of NF‐κB
Abstract
This study investigated if EX‐527 has an anti‐tumour effect in SKOV‐3 and OVCAR‐3 ovarian cancer (OC) cell lines and if this effect involves the SIRT1/NF‐κB axis. Cells were cultured in the presence or absence of EX‐527, a selective SIRT‐1 inhibitor. Exendin‐4 significantly induced cell death in both cell lines and inhibited cell migration and invasion. Also, it decreased protein levels of Bcl‐2, MMP‐9, and ICAM‐1 and increased those of Bax, cyclin D1 and cleaved caspase‐3. Mechanistically, Exendin‐4 increased the activity and nuclear accumulation of SIRT1 and decreased nuclear levels of NF‐κB p65; acetylated levels of NF‐κB p65, and cytoplasmic levels of p‐IKKα and p‐IκBα. EX‐527 partially ameliorated the effect of Exendin‐4 on cell death, migration, and invasion, as well as on the expression of Bcl‐2, MMP‐9, Bax, cleaved caspase‐3 and ICAM‐1. In addition, EX‐527 did not affect the levels of nuclear p65 and p‐p65 (Ser536); p‐IκBα (Ser32) and p‐IKKαβ. In conclusion, Exendin‐4 can suppress OC by inhibiting NF‐kB through SIRT1 dependent and independent mechanisms.
