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南蛇藤提取物通过转化生长因子-β信号通路抑制胃癌上皮-间质转化过程。

Celastrus orbiculatus Extract Inhibits the Epithelial-Mesenchymal Transition Process by Transforming Growth Factor-β Signaling Pathway in Gastric Cancer.

机构信息

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China.

The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, PR China.

出版信息

Anticancer Agents Med Chem. 2022;22(12):2282-2291. doi: 10.2174/1871520621666211210145011.

Abstract

BACKGROUND

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 (COE) has been shown to inhibit the activity of a variety of tumors. In this study, we examined the inhibition of the epithelial-mesenchymal transition (EMT) process in gastric cancer cells by COE through the transforming growth factor-β (TGF-β) signaling pathway.

METHODS

COE was first diluted to various concentrations and then used to treat SGC-7901, BGC-823, MGC-803, and AGS cells. Cell proliferation was assessed by an MTT (thiazole blue) assay. Transwell assays were used to assess cell invasion and migration. The 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 of the drug on the expression of EMT and Smad2/3 signaling pathway-related proteins.

RESULTS

We found that COE inhibited the migration and invasion of AGS gastric cancer cells in a dose-dependent manner. Consequently, COE decreased the expression of EMT-related proteins and proteins related to the Smad2/3 signaling pathway in gastric cancer cells, inhibiting the migration and invasion of gastric cancer cells, and this effect occurred through the TGF-β signaling pathway.

CONCLUSION

We investigated that COE could inhibit the proliferation of gastric cancer cells and inhibit invasion and metastasis by inhibiting the EMT process at the molecular level and its effect on the TGF-β signaling pathway.

摘要

背景

胃癌是第五大常见肿瘤,在各种恶性肿瘤中死亡率排名第三,患者的生存率较低。杠柳提取物(COE)已被证明能抑制多种肿瘤的活性。在这项研究中,我们通过转化生长因子-β(TGF-β)信号通路,研究了 COE 对胃癌细胞上皮间质转化(EMT)过程的抑制作用。

方法

首先将 COE 稀释至不同浓度,然后用于处理 SGC-7901、BGC-823、MGC-803 和 AGS 细胞。噻唑蓝(MTT)法评估细胞增殖。Transwell 实验评估细胞侵袭和迁移。高内涵成像技术进一步观察药物对细胞侵袭和迁移的影响。Western blot 法评估药物对 EMT 和 Smad2/3 信号通路相关蛋白表达的影响。

结果

我们发现 COE 呈剂量依赖性抑制 AGS 胃癌细胞的迁移和侵袭。因此,COE 降低了胃癌细胞中 EMT 相关蛋白和 Smad2/3 信号通路相关蛋白的表达,抑制了胃癌细胞的迁移和侵袭,这种作用是通过 TGF-β 信号通路发生的。

结论

我们研究发现,COE 可以通过抑制 EMT 过程及其对 TGF-β 信号通路的作用,在分子水平上抑制胃癌细胞的增殖,并抑制其侵袭和转移。

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