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

Oncol Lett. 2015 May;9(5):2381-2387. doi: 10.3892/ol.2015.2988. Epub 2015 Feb 26.

Abstract

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.

Keywords: cyclopamine; gastric cancer epithelial-mesenchymal transition; hedgehog signaling pathway; resveratrol.