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

Sha M, Ye J, Zhang LX, Luan ZY, Chen YB - Cancer Cell Int. (2013)

Bottom Line: Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity.In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China. tzrmyy5211@163.com.

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.

No MeSH data available.


Related in: MedlinePlus

Celastrol stimulates miR-146a expression in gastric cancer cells. The expression of miR-146a was significantly increased after celastrol treatment for 12 h in BGC-823, SGC-7901 and MGC-803 cells. *P < 0.05 vs. control group.
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Figure 2: Celastrol stimulates miR-146a expression in gastric cancer cells. The expression of miR-146a was significantly increased after celastrol treatment for 12 h in BGC-823, SGC-7901 and MGC-803 cells. *P < 0.05 vs. control group.

Mentions: To further identify the mechanism for celastrol inhibition of BGC-823, SGC-7901 and MGC-803 cells growth, we performed real-time PCR to detect miR-146a expression after treated with 2 μM of celastrol for 12 h. As shown in Figure 2, celastrol treatment significantly increased the expression of miR-146a in these cells (P < 0.01). However, celastrol can not significantly induce miR-146a expression in GES-1 cells.


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

Sha M, Ye J, Zhang LX, Luan ZY, Chen YB - Cancer Cell Int. (2013)

Celastrol stimulates miR-146a expression in gastric cancer cells. The expression of miR-146a was significantly increased after celastrol treatment for 12 h in BGC-823, SGC-7901 and MGC-803 cells. *P < 0.05 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672015&req=5

Figure 2: Celastrol stimulates miR-146a expression in gastric cancer cells. The expression of miR-146a was significantly increased after celastrol treatment for 12 h in BGC-823, SGC-7901 and MGC-803 cells. *P < 0.05 vs. control group.
Mentions: To further identify the mechanism for celastrol inhibition of BGC-823, SGC-7901 and MGC-803 cells growth, we performed real-time PCR to detect miR-146a expression after treated with 2 μM of celastrol for 12 h. As shown in Figure 2, celastrol treatment significantly increased the expression of miR-146a in these cells (P < 0.01). However, celastrol can not significantly induce miR-146a expression in GES-1 cells.

Bottom Line: Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity.In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China. tzrmyy5211@163.com.

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.

No MeSH data available.


Related in: MedlinePlus