Title:Resveratrol Counteracts Hypoxia-Induced Gastric Cancer Invasion and EMT through Hedgehog Pathway Suppression
Volume: 20
Issue: 9
Author(s): Qin-Hong Xu, Ying Xiao, Xu-Qi Li*, Lin Fan*, Can-Can Zhou, Liang Cheng, Zheng-Dong Jiang and Guang-Hui Wang
Affiliation:
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an 710061, Shaanxi,China
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an 710061, Shaanxi,China
Keywords:
Gastric cancer, hypoxia, epithelial-mesenchymal transition, resveratrol, HIF-1α, hedgehog.
Abstract: Background: Gastric Cancer (GC) is one of the most malignant and lethal tumors worldwide. The
hypoxic microenvironment is correlated with GC cell invasion, metastasis and Epithelial-Mesenchymal Transition
(EMT). Resveratrol is a compound extracted from various plants, including grapes, berries, and some traditional
Chinese medicines. Recently, the anticancer properties of resveratrol against many cancers have been reported in a
range of studies. However, the exact mechanism through which resveratrol prevents GC invasion and metastasis
under hypoxic conditions remains unclear.
Objective: The objective of this study is to show to what extent resveratrol could inhibit the hypoxia-induced malignant
biological behavior of GC.
Methods: SGC-7901 cells were cultured in a consistent 3% O2 hypoxic condition or 21% O2 normal condition for 48
hours to establish an in vitro hypoxia model. Western blot and qRT-PCR were used to detect EMT markers of SGC-
7901 cells, including E-cadherin, HIF-1a, Vimentin, etc. Transwell Matrigel Invasion Assays were used to test the
invasive ability of SGC-7901 cells. The siRNA targeting Gli-1 showed its role in hypoxia-induced EMT and invasion
of SGC-7901 cells.
Results: Resveratrol was found to significantly decrease HIF-1α protein levels induced by hypoxia in SGC-7901
cells. HIF-1α accumulation was found to promote cell proliferation, migration, and invasive capacities in addition to
EMT changes through the activation of the Hedgehog pathway. These effects were found to be reversed by resveratrol.
Conclusion: Therefore, these data indicate that resveratrol may serve as a potential anticancer agent for the treatment
of GC, even in a hypoxic tumor microenvironment.
