Effect of Helicobacter pylori virulence factor CagA-mediated activation of ERK signaling pathway on proliferation and apoptosis of gastric cancer cells / 吉林大学学报(医学版)

ABSTRACT

Objective: To explore the effect of Helicobacter pylori virulence factor cytotoxin-associated gene A protein (CagA) on the extracellular regulated protein kinase (ERK) signaling pathway, and to elucidate the carcinogenesis mechanism of CagA. Methods: The pcDNA3. 1/CagA eukaryotic expression vector was constructed, and the gastric cancer AGS cells were divided into blank control group (blank vector transfection), CagA transfection group (GZ7/CagA transfection), and CagA + ERKi group (ERK1/2 inhibitor pretreatment + GZ7/CagA transfection). The expression levels of CagA, phosphorylated ERK (p-ERK), total ERK (T-ERK), B-lymphocytoma-2 (Bcl-2), Bcl-2-related X protein (Bax) and cleaved caspase-3 proteins in the cells in various groups were determined by Western blotting method. The activities of AGS cells in various groups were determined by CCK-8 method, and the apoptotic rates of AGS cells were determined by flow cytometry. Results: Compared with blank control group, the expression levels of CagA, p-ERK, and Bel-2 proteins in CagA transfection group were significantly increased (P<0. 01), and the expression levels of Bax and cleaved caspase-3 proteins were significantly decreased (P<0. 01). Compared with CagA transfection group, the expression levels of p-ERK and Bel-2 proteins in CagA+ERKi group were significantly decreased (P<0. 01), and the expression levels of Bax and cleaved caspase-3 proteins were significantly increased (P<0. 01). Compared with CagA transfection group, the activities of gastric cancer cells in CagA + ERKi group at different time points were significantly decreased (P< 0. 01). Compared with CagA transfection group, the apoptotic rate of gastric cancer cells in CagA + ERKi group was significantly increased (P<0. 05). Conclusion: Helicobacter pylori virulence factor CagA can inhibit the proliferation of gastric cancer cells and promote the apoptosis of gastric cancer cells, and its mechanism may be related to the activation of ERK signaling pathway by CagA.