28-Hydroxy-3-oxoolean-12-en-29-oic Acid, a Triterpene Acid from Celastrus Orbiculatus Extract, Inhibits the Migration and Invasion of Human Gastric Cancer Cells In Vitro

28-Hydroxy-3-oxoolean-12-en-29-oic Acid, a Triterpene Acid from Celastrus Orbiculatus Extract, Inhibits the Migration and Invasion of Human Gastric Cancer Cells In Vitro
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28-Hydroxy-3-oxolean-12-en-29-oic Acid,一种来自南蛇藤提取物的三萜酸,在体外抑制人胃癌细胞的迁移和侵袭

DOI:
10.3390/molecules24193513
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发表时间:
2019-10-01
期刊:
影响因子:
4.6
通讯作者:
Liu, Yanqing
Liu, Yanqing
中科院分区:
化学2区
文献类型:
--
作者:
Chu, Zewen;Wang, Haibo;Liu, Yanqing

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胃癌是各种恶性肿瘤中发病率第五高、死亡率第三高的肿瘤,患者生存率较低。蛇芹提取物已被证明具有抑制多种肿瘤活性的作用。本研究探讨了环青藤提取物中齐墩烷型三萜酸28-羟基-3-氧果酸-12-烯-29-酸分子对胃癌细胞侵袭转移的抑制作用,并确定其作用机制。28-羟基-3-氧库林-12-烯-29-酸先稀释至不同浓度,然后用于SGC-7901和BGC-823细胞。用MTT(噻唑蓝)法测定细胞增殖。Transwell和伤口愈合试验用于评估细胞侵袭和迁移。采用高含量成像技术进一步观察药物对细胞侵袭和迁移的影响。Western blotting检测对基质金属蛋白酶(MMPs)表达的影响以及对上皮-间质转化(EMT)相关蛋白和磷酸化相关蛋白的影响。我们发现28-羟基-3-oxoolean-12-en-29-oic酸对SGC-7901和BGC-823胃癌细胞的迁移和侵袭具有剂量依赖性。因此,28-羟基-3-oxoolean-12-en-29-oic酸可降低胃癌细胞中emt相关蛋白和MMPs的表达,降低蛋白磷酸化,抑制胃癌细胞的迁移和侵袭。
Gastric cancer is the fifth most common tumor and has the third-highest mortality rate among various malignant tumors, and the survival rate of patients is low. Celastrus orbiculatus extract has been shown to inhibit the activity of a variety of tumors. This study explored the inhibitory effect of the oleanane-type triterpenoid acid 28-hydroxy-3-oxoolean-12-en-29-oic acid molecule from Celastrus orbiculatus extract on gastric cancer cell invasion and metastasis and determined its mechanism. 28-Hydroxy-3-oxoolean-12-en-29-oic acid was first diluted to various concentrations and then used to treat SGC-7901 and BGC-823 cells. Cell proliferation was assessed by an MTT (thiazole blue) assay. Transwell and wound healing assays were used to assess cell invasion and migration. High-content imaging technology was used to further observe the effects of the drug on cell invasion and migration. Western blotting was used to assess the effects on the expression of matrix metalloproteinases (MMPs) and the effects on epithelial–mesenchymal transition (EMT)-related proteins and phosphorylation-related proteins. We found that 28-Hydroxy-3-oxoolean-12-en-29-oic acid inhibited the migration and invasion of SGC-7901 and BGC-823 gastric cancer cells in a dose-dependent manner. Consequently, 28-hydroxy-3-oxoolean-12-en-29-oic acid decreased the expression of EMT-related proteins and MMPs in gastric cancer cells and reduced protein phosphorylation, inhibiting the migration and invasion of gastric cancer cells.