Knockdown of microsomal glutathione S-transferase 1 inhibits lung adenocarcinoma cell proliferation and induces apoptosis - 30/11/19
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Graphical abstract |
Highlights |
• | MGST1 was highly expressed in LUAD tissues. |
• | MGST1 expression positively correlated with AJCC stage and poor overall survival. |
• | Knocking down MGST1 inhibited LUAD cell proliferation and induced cell apoptosis. |
• | MGST1 knockdown inactivated AKT/GSK-3β pathway signaling in LUAD cells. |
Abstract |
Background |
Lung cancer has been the most common cancer worldwide. Microsomal glutathione S-transferase 1 (MGST1) has been reported to play vital roles in oxidative stress, tumor occurrence and drug resistance. However, the biological function and molecular mechanism of MGST1 in lung adenocarcinoma (LUAD) has not yet been elucidated.
Methods |
The expression of MGST1 in LUAD tissues and cell lines was evaluated by immunohistochemistry and western blotting, respectively. MGST1 was knocked down by shRNA lentivirus. Cell proliferation was evaluated by MTS, colony formation and EdU assays. Apoptosis was detected by flow cytometry. The potential molecules involved in cell proliferation and apoptosis were examined by western blotting. Finally, the effect of MGST1 on tumor growth in vivo was evaluated in a nude mouse xenograft model.
Results |
TCGA database analysis and immunohistochemistry demonstrated that MGST1 was highly expressed in LUAD tissues. MGST1 expression in LUAD was correlated with AJCC stage and poor overall survival of patients. MGST1 knockdown significantly inhibited LUAD cell proliferation and induced apoptosis. Mechanistic analyses revealed that MGST1 knockdown might inhibit cell proliferation by inactivating the AKT/GSK-3β pathway signaling and promote cell apoptosis by regulating the mitochondrial apoptosis pathway related proteins. Moreover, knockdown of MGST1 suppressed tumor growth in vivo.
Conclusions |
MGST1 plays an important role in LUAD tumorigenesis and might serve as a potential prognostic factor and therapeutic target in LUAD.
Le texte complet de cet article est disponible en PDF.Keywords : Microsomal glutathione transferase-1, Lung adenocarcinoma, Proliferation, Apoptosis, AKT/GSK-3β
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Article 109562- janvier 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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