[摘 要] 目的：探究错配修复蛋白2（MSH2）在胃癌中表达和其与患者临床特征的关系及其对胃癌细胞恶性生物学行为的作 用及机制。方法：收集2020年5月至2022年7月期间在邢台市人民医院收治的40例胃癌患者的癌组织和配对癌旁组织及患者 的一般临床资料。常规培养正常人胃黏膜上皮细胞GES-1和胃癌细胞AGS、MKN45和BGC-823，用转染试剂分别将sh-NC、 shMSH2-1和shMSH2-2慢病毒载体转染至AGS和MKN45细胞中，实验分为sh-NC、shMSH2-1和shMSH2-2组。CCK-8法、克 隆形成实验、EdU染色、Transwell小室实验分别检测各组AGS和MKN45细胞的增殖、迁移和侵袭能力。构建裸鼠MKN45细胞 移植瘤模型，观察敲减MSH2对移植瘤生长的影响。WB法检测各组细胞中及移植瘤组织中 MSH2、PI3K/AKT/mTOR通路、上皮 间质转化相关蛋白的表达。结果：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良均有关 联（均P < 0.001）；在AGS和MKN45细胞中成功地敲减了MSH2的表达（P < 0.001）；敲减 MSH2均能显著抑制AGS和MKN45细 胞的活力、EdU染色阳性率、克隆形成能力、迁移及侵袭能力和移植瘤的生长（均P < 0.001）；均能显著抑制AGS和MKN45细胞 和MKN45移植瘤组织中MSH2蛋白、PI3K/AKT/mTOR通路相关蛋白、N-cadherin蛋白的表达（均P < 0.001），促进E-cadherin蛋 白的表达（P < 0.001）。结论：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良有关联，敲减 MSH2表达通过抑制PI3K/AKT/mTOR通路调控AGS和MKN45细胞的恶性生物学行为，MSH2可能是胃癌治疗的潜在靶点。

[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.

2019年度河北省人才工程培养资助项目（No.A201903017）；2021年度邢台市科技计划自筹经费项目（No.2021ZC128）