Metformin regulates proliferation and apoptosis of gastric cancer stem cells through the Akt pathway

doi:10.3969/j.issn.2095-4344.1544

Abstract

Abstract:

BACKGROUND: Metformin can inhibit the proliferation of a variety of tumor stem cells, including gastric cancer stem cells, and target gastric cancer stem cells to provide a new idea for the clinical treatment of gastric cancer. However, the role and possible mechanism of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the proliferation of gastric cancer stem cells have not yet been reported.
OBJECTIVE: To investigate the effect of metformin on the proliferation and apoptosis of gastric cancer stem cells as well as the role of PI3K/Akt signaling pathway.
METHODS: Gastric cancer stem cells were isolated and cultured from human gastric cancer cell line SGC7901. (1) Metformin with different concentrations (1, 5, 10 mmol/L) was used to treat gastric cancer stem cells for 24, 48 and 72 hours. MTT was used to detect cell proliferation, flow cytometry was used to detect cell apoptosis and R-qPCR was used to detect the expressions of PI3K and Akt mRNA in the cells. (2) The gastric cancer stem cells were treated with 8 mmol/L metformin and 100 mg/L Akt activator (insulin growth factor-1). Western blot assay was used to detect the expression of PI3K, Akt and phosphorylated Akt (p-Akt) protein. The proliferation activity and apoptosis of the cells were detected by MTT and flow cytometry, respectively.
RESULTS AND CONCLUSION: Gastric cancer stem cells can be isolated from human gastric cancer SGC7901 cells by adding exogenous growth factors in serum-free conditions. The proliferative activity of gastric cancer stem cells decreased with the increasing concentration of metformin and prolonged time (P < 0.05). The apoptosis rate of gastric cancer stem cells increased with the increase of metformin concentration and the prolongation of time (P < 0.05). The expression of Akt mRNA in gastric cancer stem cells decreased with the increasing concentration of metformin and prolonged time (P < 0.05), but the expression of PI3K mRNA showed no marked reduction. Compared with metformin, the Akt activator increased the activity of gastric cancer stem cells, decreased the cell apoptosis, and elevated the expression of Akt and p-Akt (P < 0.05). These findings indicate that metformin can inhibit proliferation and induce apoptosis of gastric cancer stem cells by inhibiting the Akt signaling pathway.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Stomach Neoplasms, Neoplastic Stem Cells, Metformin, Cell Proliferation, Apoptosis, Tissue Engineering

CLC Number:

Zha Luqin, Han Bengao, Zhang Chaojie. Metformin regulates proliferation and apoptosis of gastric cancer stem cells through the Akt pathway[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(5): 657-662.

Figures/Tables 5

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