Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China.
Cancer Cell Int. 2013 May 27;13(1):50. doi: 10.1186/1475-2867-13-50.
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.
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.
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.
In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.
雷公藤红素是一种植物三萜，已知在抑制胃癌细胞增殖和诱导细胞凋亡方面发挥重要作用。本研究旨在探讨雷公藤红素诱导胃癌细胞凋亡的作用机制。
我们通过 Western blot 和荧光素酶报告基因检测评估了雷公藤红素对胃癌细胞 NF-κB 信号通路的影响。实时 PCR 用于评估雷公藤红素对 miR-146a 表达的影响，并用 miR-146a 模拟物评估过表达 miR-146a 是否能影响 NF-κB 活性。最后，用 miR-146a 抑制剂评估 miR-146a 对雷公藤红素诱导的抗肿瘤活性的影响。
雷公藤红素呈剂量依赖性降低胃癌细胞活力。雷公藤红素还降低了 IκB 磷酸化、核 P65 蛋白水平和 NF-κB 活性。此外，雷公藤红素可以增加 miR-146a 的表达，上调 miR-146a 的表达可以抑制 NF-κB 活性。更为重要的是，下调 miR-146a 的表达可以逆转雷公藤红素对胃癌细胞 NF-κB 活性和凋亡的影响。
在这项研究中，我们证明了雷公藤红素对凋亡的作用是由于 miR-146a 抑制 NF-κB 活性所致。
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