Xu Qin-Hong, Xiao Ying, Li Xu-Qi, Fan Lin, Zhou Can-Can, Cheng Liang, Jiang Zheng-Dong, Wang Guang-Hui
Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Anticancer Agents Med Chem. 2020;20(9):1105-1114. doi: 10.2174/1871520620666200402080034.
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.
The objective of this study is to show to what extent resveratrol could inhibit the hypoxia-induced malignant biological behavior of GC.
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.
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.
Therefore, these data indicate that resveratrol may serve as a potential anticancer agent for the treatment of GC, even in a hypoxic tumor microenvironment.
胃癌（GC）是全球最具恶性和致死性的肿瘤之一。缺氧微环境与胃癌细胞的侵袭、转移及上皮-间质转化（EMT）相关。白藜芦醇是从多种植物中提取的一种化合物，包括葡萄、浆果及一些传统中药。最近，一系列研究报道了白藜芦醇对多种癌症的抗癌特性。然而，白藜芦醇在缺氧条件下预防胃癌侵袭和转移的确切机制仍不清楚。
本研究的目的是揭示白藜芦醇在多大程度上可以抑制缺氧诱导的胃癌恶性生物学行为。
将SGC-7901细胞在3% O₂缺氧条件或21% O₂正常条件下培养48小时，以建立体外缺氧模型。采用蛋白质免疫印迹法（Western blot）和实时定量聚合酶链反应（qRT-PCR）检测SGC-7901细胞的EMT标志物，包括E-钙黏蛋白、缺氧诱导因子-1α（HIF-1α）、波形蛋白等。采用Transwell基质胶侵袭实验检测SGC-7901细胞的侵袭能力。靶向Gli-1的小干扰RNA（siRNA）显示其在缺氧诱导的SGC-7901细胞EMT和侵袭中的作用。
发现白藜芦醇可显著降低缺氧诱导的SGC-7901细胞中HIF-1α蛋白水平。发现HIF-1α的积累除了通过激活Hedgehog信号通路引起EMT变化外，还促进细胞增殖、迁移和侵袭能力。发现白藜芦醇可逆转这些作用。
因此，这些数据表明，即使在缺氧的肿瘤微环境中，白藜芦醇也可能作为一种潜在的抗癌药物用于治疗胃癌。
