Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-kappaB activity

Background: Celastrol, a plant triterpene, is known to play important role in inhibiting proliferation and inducing apoptosis of gastric cancer cells. In the present study, the mechanism of celastrol on gastric cancer cells apoptosis was examined. Methods: We assessed effect of celastrol on NF-kappaB signaling pathway in gastric cancer cells using western blot and luciferase reporter assay. The real-time PCR was used to evaluate the effect of celastrol on miR-146a expression, and miR-146a mimic to evaluate whether over-expression of miR-146a can affect NF-kappaB activity. Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor. Results: Celastrol decreased gastric cancer cells viability in a dose-dependent. Celastrol also reduced IkappaB phosphorylation, nuclear P65 protein levels and NF-kappaB activity. Furthermore, Celastrol could increase miR-146a expression and up-regulation of miR-146a expression could suppress NF-kappaB activity. More important, down-regulation of miR-146a expression can reverse the effect of celastrol on NF-kappaB activity and apoptosis in gastric cancer cells. Conclusions: In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-kappaB activity.

via Cancer Cell International