Published in:
Open Access
01-12-2013 | Primary research
Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-κB activity
Authors:
Min Sha, Jun Ye, Li-xin Zhang, Zheng-yun Luan, Ya-bao Chen
Published in:
Cancer Cell International
|
Issue 1/2013
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Abstract
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-κB 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-κB 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 IκB phosphorylation, nuclear P65 protein levels and NF-κB activity. Furthermore, Celastrol could increase miR-146a expression and up-regulation of miR-146a expression could suppress NF-κB activity. More important, down-regulation of miR-146a expression can reverse the effect of celastrol on NF-κB 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-κB activity.