Chronic inflammation resulting from Helicobacter pylori (H. pylori) infection, the major risk factor for gastric cancer, results in increased release of reactive oxygen species (ROS), promoting oxidative stress and DNA damage. APE1 endonuclease, a key component of the base excision repair (BER) pathway, is responsible for the repair of damage induced by ROS. However, the APE1 gene and other DNA damage response (DDR) genes are still poorly understood in gastric cancer. Thus, we aimed to investigate whether the silencing of APE1 by shRNA can interfere with the survival of AGS gastric cancer cells after treatment with hydrogen peroxide (H₂O₂) and/or H. pylori extract (HPE) and its relation with the expression of DDR genes (ATM, ATR, and H2AX) and miRNAs that target DDR genes. In the AGS cells expressing APE1, isolated or combined treatment with H₂O₂ and HPE promoted a slight increase in the cell proliferation and increased the levels of intracellular ROS and DNA double strand breaks (DSBs) indicated by ©H2AX foci, a reduction in the proportion of cells in the G0/G1 phase and an increase in the initial apoptosis rate. Moreover, upregulation of APE1, ATR, miR-15a, miR-21, miR-24 and miR-421 and downregulation of ATM and H2AX was observed. In silenced AGS cells after treatment with H₂O₂ alone or combined with HPE, we observed an increase in the cell proliferation rate and the levels of intracellular ROS and DSBs and a reduction in the proportion of cells in S and G2/M phase arrest, leading to late apoptosis. APE1 knockdown also caused a reduction in the expression of ATM and miR-421, while ATR expression was increased. Based on our results, APE1 knockdown may promote changes in cellular processes by increasing genomic instability, leading to G2/M arrest and cell apoptosis, so it may be a promising strategy for controlling tumor progression.

幽门螺杆菌（H. pylori）感染是胃癌的主要危险因素，它引起的慢性炎症导致活性氧（ROS）释放增加，促进了氧化应激和DNA损伤。APE1核酸内切酶是碱基切除修复（BER）途径的关键组成部分，负责修复由ROS引起的损伤。然而，APE1基因和其他DNA损伤反应（DDR）基因在胃癌中仍然知之甚少。因此，我们旨在研究shRNA对APE1的沉默是否会干扰过氧化氢（H ₂ O ₂）和/或幽门螺杆菌治疗后AGS胃癌细胞的存活。提取物（HPE）及其与DDR基因（ATM，ATR和H2AX）和靶向DDR基因的miRNA表达的关系。在表达APE1的AGS细胞中，用H ₂ O ₂和HPE分离或联合处理可促进细胞增殖的轻微增加，并增加©H2AX病灶指示的细胞内ROS和DNA双链断裂（DSB）的水平，降低了细胞处于G0 / G1期的比例和初始凋亡率的增加。此外，APE1，ATR， miR-15a，miR-21，miR-24和miR-421的上调以及ATM和H2AX的下调被观测到。在单独用H ₂ O ₂或与HPE结合处理后的沉默的AGS细胞中，我们观察到细胞增殖速率和细胞内ROS和DSB的水平增加，并且S和G2 / M期停滞的细胞比例减少，导致晚期细胞凋亡。APE1敲低还导致ATM和miR-421的表达减少，而ATR的表达增加。根据我们的结果，APE1敲低可能通过增加基因组不稳定性来促进细胞过程的变化，从而导致G2 / M阻滞和细胞凋亡，因此它可能是控制肿瘤进展的一种有前途的策略。