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28-hydroxy-3-oxoolan-12-en-2-oic acid and miR-451 synergistically inhibit the proliferation and migration of gastric cancer AGS cells and its possible mechanism
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Abstract:
Objective: To explore the synergistic effect of 28-hydroxy-3-oxoolean-12-en-2-oic acid and miR-451 on the proliferation and migration of human gastric cancer AGS cells and its possible molecular mechanism. Methods: AGS cells were infected with miR-451 overexpression lentivirus and induced with DOX (10 or 100 ng/ml) for 24 h to construct AGS/miR-451+ cells overexpressing miR-451. AGS/miR-451+ cells were treated with 28-hydroxy-3-oxoolean-12-en-2-oic acid of 10, 20, 40, 80, 160 μmol/L. The changes in proliferation and migration ability of cells were detected by the MTT method and the scratch test, respectively; WB method was used to detect the changes in the expression levels of mTOR signaling pathway-related and apoptosis-related proteins in cells. Results:AGS/miR-451+ cells overexpressing miR-451 were successfully constructed. Compared with the untreated control group, the proliferation inhibition rate of AGS/miR-451+ cells in the 28-hydroxy-3-oxoolean-12-en-2-oic acid treatment group increased in a time[1]and concentration-dependent manner (P<0.05 or P<0.01), while the cell migration rate was significantly reduced (P<0.05 or P<0.01). In the cells treated with 28-hydroxy-3-oxoolean-12-en-2-oic acid, the expression of mTOR signaling pathway-related proteins was reduced (P<0.05 or P<0.01); among the apoptosis pathway-related proteins, the expression of Bcl2 was decreased, but the expression of BAX,caspase-3, caspase-1, and cytochrome c was increased (P<0.05 or 0.01). Conclusion: The 28-hydroxy-3-oxoolean-12-en-2-oic and miR-451 can synergistically inhibit the proliferation and migration of human gastric cancer AGS cells. The mechanism may be related to their regulation of apoptosis signaling pathway- and mTOR signaling pathway-related proteins.
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Project Supported:
Project supported by the Natural Science Foundation of Jiangsu Province (No. BK20171290), and the Major Programs of Natural Science Foundation of Higher Education in Jiangsu Province (No. 19KJA480003)
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