Abstract

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.

Highlights

  • Gastric cancer (GC) is one of the most common malignancies in the world, with mortality worldwide

  • This study investigated whether the oleanane-type triterpenoid acid 28-hydroxy-3oxoolean-12-en-29-oic acid can inhibit the invasion and metastasis of gastric cancer cells and explored its potential molecular mechanism

  • We investigated whether 28-hydroxy3-oxoolean-12-en-29-oic acid affects the invasion and metastasis of gastric cancer cells

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Summary

Introduction

Gastric cancer (GC) is one of the most common malignancies in the world, with mortality worldwide. Patients with early gastric cancer have a good prognosis, and the curative effect of radical surgery is significant. Invasion and metastasis are important causes of death in gastric cancer patients, and the mechanism of tumor invasion and metastasis is very complicated. These processes mainly involve epithelial–mesenchymal transition (EMT), CAM secretion, extracellular matrix (ECM). Continued understanding of the occurrence and mechanism of tumor invasion and metastasis will definitely play an extensive role in the search for and development of effective antitumor drugs and will provide new ideas and approaches for the prevention of cancer. The Celastrus orbiculatus oleanane-type triterpenoid acid 28-hydroxy-3-oxoolean-12-en-29-oic acid is the most sensitive, so this component was selected for further study. This study provides a more solid theoretical and experimental basis for further development of Celastrus orbiculatus Thunb. extract components as antitumor drugs

Results
PerkinElmer Operetta CLS High-Content Imaging System Analysis
Discussion
Materials and Methods
Reagents
Cell Culture
Cell Viability Assay
Cell Invasion and Migration Assay
Western Blot Analysis
Statistical Analysis
Full Text
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