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.