Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis
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DOI:
10.3892/ol.2015.2988
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发表时间:
2015-05-01
期刊:
影响因子:
2.9
通讯作者:
Peng, Qiong
Peng, Qiong
中科院分区:
医学4区
文献类型:
--
作者:
Gao, Qian;Yuan, Yuan;Peng, Qiong

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Hedgehog(Hh)信号通路对脊椎动物的发育、体内平衡过程和肿瘤发生至关重要。上皮-间质转化(EMT)是上皮细胞向间质样细胞转化的过程,这反过来又促进了肿瘤的转移和侵袭。白藜芦醇是一种天然多酚化合物,存在于葡萄、各种浆果、花生和其他植物中。大量研究表明,Hh信号通路能够调节EMT,白藜芦醇能够抑制肿瘤的侵袭和转移。此外,一些研究表明,白藜芦醇可以抑制Hh信号通路和EMT在胃癌以外的癌症。本研究旨在探讨白藜芦醇对胃癌细胞Hh信号通路及EMT的抑制作用。用不同浓度的白藜芦醇或环巴胺处理胃癌SGC-7901细胞。使用MTT测定法评估细胞的活力。逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法检测Hh信号通路的关键组分Gli-1和EMT的关键组分Snail、E-cadherin和N-cadherin的表达。通过细胞划痕试验观察细胞的侵袭和转移。RT-PCR和Western blotting显示,与对照组相比,白藜芦醇和环巴胺组Gli-1、Snail和N-cadherin表达降低,E-cadherin表达降低,提示白藜芦醇和环巴胺抑制Hh通路和EMT。increase.in MTT法检测表明,白藜芦醇和环巴胺处理后,SGC-7901细胞的存活率显著降低,并呈浓度依赖性。细胞划痕实验显示白藜芦醇组和环巴胺组的细胞侵袭和转移较慢。这些结果表明白藜芦醇能够抑制Hh信号通路和EMT,抑制胃癌细胞的体外侵袭和转移。
The hedgehog (Hh) signaling pathway is vital to vertebrate development, the homeostatic process and tumorigenesis. Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, which in turn promotes cancer metastasis and invasion. Resveratrol is a natural polyphenolic compound found in grapes, a variety of berries, peanuts and other plants. Numerous studies have demonstrated that the Hh signaling pathway is able to regulate the EMT, and that resveratrol can suppress carcinoma invasion and metastasis. In addition, certain studies have indicated that resveratrol can inhibit the Hh signaling pathway and EMT in cancers other than gastric cancer. The purpose of the present study was to investigate the inhibitory effect of resveratrol on the Hh signaling pathway and EMT in gastric cancer in vitro. Gastric cancer SGC-7901 cells were treated with resveratrol or cyclopamine at different concentrations. The viability of the cells was assessed using an MTT assay. The expression of Gli-1, a key component of the Hh signaling pathway, and Snail, E-cadherin and N-cadherin, key components of EMT, was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The invasion and metastasis of the cells were observed by performing a cell scratch test. The RT-PCR and western blotting showed a decrease in Gli-1, Snail and N-cadherin expression, and an increase.in E-cadherin expression in the resveratrol and cyclopamine group compared with the control group, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine. The MTT assay indicated that the viability of the SGC-7901 cells was significantly decreased in a concentration-dependent manner following resveratrol and cyclopamine treatment. The cell scratch test showed slower cell invasion and metastasis in the resveratrol and cyclopamine groups. These findings indicated that resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro.