The tumor suppressor gene phosphatase and tensin homolog (PTEN) in PI3K/Akt/mTOR pathway is essential in inhibiting tumor growth and metastasis. However, whether the mutation of PTEN gene could induce tumorigenesis and impact the treatment of gastric cancer is still unclear. The purpose of the study was to investigate the combined treatment of gastric tumorigenesis using Rapamycin and Fluorouracil (5-Fu) through interfering with the Akt/mTOR pathway in a mouse model with PTEN conditional deletion. Three groups of mice were exposed for 5 days to Rapamycin and 5-Fu separately and together. The gene expression of the Akt/mTOR pathway, the protein expression of caspase-3 and p-Akt, p-S6K and p-4EBP1, and the pathological changes in stomachs were analyzed. Our study demonstrates that the conditional PTEN deletion in the cells of glandular stomach induces hyperplastic gastric tumors in mice. The combined Rapamycin administration with 5-Fu resulted in better outcomes than their separate administration for the treatment of gastric cancer by inhibiting the mTOR signal pathway. Our study indicates that Rapamycin has a synergistic interaction with chemotherapeutic 5-Fu, and demonstrates a potential therapeutic combination treatment on glandular stomach tumor with PTEN functional absence or aberrantly activated Akt/mTOR pathway. It provides important insights into the inhibition of the Akt/mTOR pathway in gastric cancer clinical therapy.

PI3K/Akt/mTOR通路中的抑癌基因磷酸酶和张力蛋白同源物（PTEN）对于抑制肿瘤生长和转移至关重要。然而，PTEN基因的突变是否会诱导肿瘤发生并影响胃癌的治疗尚不清楚。本研究的目的是通过在具有PTEN的小鼠模型中通过干扰 Akt/mTOR 通路，研究使用雷帕霉素和氟尿嘧啶 (5-Fu) 联合治疗胃肿瘤发生。有条件的删除。三组小鼠分别和一起暴露于雷帕霉素和5-Fu 5天。分析Akt/mTOR通路基因表达、caspase-3和p-Akt、p-S6K和p-4EBP1蛋白表达及胃部病理变化。我们的研究表明，条件PTEN腺胃细胞的缺失会在小鼠中诱发增生性胃肿瘤。通过抑制 mTOR 信号通路，雷帕霉素与 5-Fu 联合给药比单独给药治疗胃癌的结果更好。我们的研究表明，雷帕霉素与化疗药物 5-Fu 具有协同作用，并证明了对 PTEN 功能缺失或异常激活的 Akt/mTOR 通路的腺性胃肿瘤的潜在治疗组合治疗。它为胃癌临床治疗中 Akt/mTOR 通路的抑制提供了重要的见解。