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Archive > Volume 32 Issue 6 > 2025,32(6):641-648. DOI:10.3872/j.issn.1007-385X.2025.06.011 Prev Next
Clinical Research
MSH2 regulating the malignant biological behavior of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway
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Abstract:
[Abstract] Objective: To investigate the expression of mismatch repair protein 2 (MSH2) in gastric cancer and its correlation with patient clinical characteristics, as well as its effects on malignant biological behaviors of gastric cancer cells and underlying mechanisms. Methods: Tumor tissues and matched adjacent tissues were collected from 40 gastric cancer patients admitted to Xingtai People's Hospital from May 2020 to July 2022, along with patient clinical data. Normal gastric mucosal epithelial cells (GES-1) and gastric cancer cell lines (AGS, MKN45, and BGC-823) were routinely cultured. The sh-NC (negative control), shMSH2-1, and shMSH2-2 lentiviral vectors were transfected into AGS and MKN45 cells, respectively, dividing the cells into sh-NC, shMSH2-1, and shMSH2-2 groups accordingly. The proliferation, migration, and invasion capabilities of AGS and MKN45 cells in each group were assessed using CCK-8 assay, colony formation assay, Edu staining, and Transwell chamber assay, respectively. A nude mouse MKN45 cell xenograft model was established to evaluate the effect of MSH2 knockdown on tumor growth. WB was performed to detect the expression of MSH2, PI3K/AKT/mTOR pathway-related proteins, and epithelial-mesenchymal transition (EMT) -related proteins in cells and xenograft tissues. Results: MSH2 was highly expressed in gastric cancer tissues and cell lines, and this elevated expression was associated with lymph node metastasis, advanced T stage, and poor histological differentiation (all P < 0.001). Successful knockdown of MSH2 expression was achieved in AGS and MKN45 cells (P < 0.001). MSH2 knockdown significantly inhibited cell viability, Edu-positive cell ratio, colony formation, migration, and invasion ability of AGS and MKN45 cells (all P < 0.001), as well as xenograft tumor growth (P < 0.001). It markedly suppressed the expression of MSH2 protein, PI3K/AKT/mTOR pathway-related proteins, and N-cadherin protein (all P < 0.001), while promoting E-cadherin expression (P < 0.001) in both AGS, MKN45 cells and MKN45 xenograft tissues. Conclusion: MSH2 is highly expressed in gastric cancer tissues and cell lines and is associated with lymph node metastasis, advanced T-stage progression, and poor histological differentiation. Knockdown of MSH2 expression suppresses the malignant biological behaviors of AGS and MKN45 cells by inhibiting the PI3K/AKT/mTOR pathway, positioning MSH2 as a potential therapeutic target for gastric cancer management.
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