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Gamma linolenic acid suppresses hypoxia-induced gastric cancer cell growth and epithelial-mesenchymal transition by inhibiting the Wnt/b-catenin signaling pathway
Affiliations- Department of Nutrition, The second hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050000, China
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Abstract
Introduction. Gastric cancer is one of the most common malignancies in China and the fifth most common cancer in the world. Gamma linolenic acid (GLA) was reported to have anti-inflammatory and anti-cancer effects. The purpose of this research was to investigate the effect and mechanism of GLA on gastric cancer cell growth under hypoxic conditions.
Material and methods. The hypoxia models of SGC-7901 and MGC-803 cells were established, and then were exposed to different concentrations of 50, 100 or 200 μM GLA. MTT assay, colony formation assay, wound healing assay and transwell assay were used to investigate the effects of GLA treatment on gastric cancer cell growth under hypoxia (1% O2). The expression of apoptosis- and epithelial-mesenchymal transition (EMT)-related proteins was detected by qPCR and western blot.
Results. GLA treatment significantly decreased viability and inhibited colony formation (p < 0.05, p < 0.01) of SGC-7901 and MGC-803 cells under hypoxia. Western blotting analysis showed that GLA treatment decreased the expression of proliferating cell nuclear antigen (PCNA), microchromosome maintenance complex component 2 (MCM-2) and anti-apoptotic protein Bcl-2, while increased the expression of pro-apoptotic proteins (Bax and Cleaved Caspase-3) (p < 0.05 and p < 0.01). In addition, Wound healing analysis and Transwell assays showed that GLA treatment inhibited the migration and invasion of SGC-7901 and MGC-803 cells in a dose-dependent manner (p < 0.01). Western blotting analysis showed that GLA treatment increased the expression of epithelial marker proteins (g-catenin and E-cadherin), while decreased the expression of stromal and extracellular matrix marker proteins (fibronectin, Snail and b-catenin) (p < 0.01). Further analyses showed that GLA treatment decreased the expression of b-catenin in Wnt/b-catenin pathway (p < 0.01). Moreover, exogenous Wnt3a reversed the inhibitory effect of GLA on b-catenin expression, and further reversed the inhibitory effect of GLA on gastric cancer cell growth and EMT markers (p < 0.05, p < 0.01).
Conclusion. These findings suggest that GLA should be tested in animal models and in clinical studies as a potentially effective bioactive phytochemical substance for the treatment of gastric cancer.
Abstract
Introduction. Gastric cancer is one of the most common malignancies in China and the fifth most common cancer in the world. Gamma linolenic acid (GLA) was reported to have anti-inflammatory and anti-cancer effects. The purpose of this research was to investigate the effect and mechanism of GLA on gastric cancer cell growth under hypoxic conditions.
Material and methods. The hypoxia models of SGC-7901 and MGC-803 cells were established, and then were exposed to different concentrations of 50, 100 or 200 μM GLA. MTT assay, colony formation assay, wound healing assay and transwell assay were used to investigate the effects of GLA treatment on gastric cancer cell growth under hypoxia (1% O2). The expression of apoptosis- and epithelial-mesenchymal transition (EMT)-related proteins was detected by qPCR and western blot.
Results. GLA treatment significantly decreased viability and inhibited colony formation (p < 0.05, p < 0.01) of SGC-7901 and MGC-803 cells under hypoxia. Western blotting analysis showed that GLA treatment decreased the expression of proliferating cell nuclear antigen (PCNA), microchromosome maintenance complex component 2 (MCM-2) and anti-apoptotic protein Bcl-2, while increased the expression of pro-apoptotic proteins (Bax and Cleaved Caspase-3) (p < 0.05 and p < 0.01). In addition, Wound healing analysis and Transwell assays showed that GLA treatment inhibited the migration and invasion of SGC-7901 and MGC-803 cells in a dose-dependent manner (p < 0.01). Western blotting analysis showed that GLA treatment increased the expression of epithelial marker proteins (g-catenin and E-cadherin), while decreased the expression of stromal and extracellular matrix marker proteins (fibronectin, Snail and b-catenin) (p < 0.01). Further analyses showed that GLA treatment decreased the expression of b-catenin in Wnt/b-catenin pathway (p < 0.01). Moreover, exogenous Wnt3a reversed the inhibitory effect of GLA on b-catenin expression, and further reversed the inhibitory effect of GLA on gastric cancer cell growth and EMT markers (p < 0.05, p < 0.01).
Conclusion. These findings suggest that GLA should be tested in animal models and in clinical studies as a potentially effective bioactive phytochemical substance for the treatment of gastric cancer.
Keywords
Gamma linolenic acid; gastric cancer; SGC-7901 cells; MGC-803 cells; hypoxia; cell growth; Wnt/b-catenin; EMT; apoptosis
About this articleTitle
Gamma linolenic acid suppresses hypoxia-induced gastric cancer cell growth and epithelial-mesenchymal transition by inhibiting the Wnt/b-catenin signaling pathway
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
117-126
Published online
2020-07-01
Page views
1953
Article views/downloads
1339
DOI
Pubmed
Bibliographic record
Folia Histochem Cytobiol 2020;58(2):117-126.
Keywords
Gamma linolenic acid
gastric cancer
SGC-7901 cells
MGC-803 cells
hypoxia
cell growth
Wnt/b-catenin
EMT
apoptosis
Authors
Yan Wang
Jian Shi
Liya Gong
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