Abstract: Background and purpose: The 6-phosphofructo-2-kinase 3 (PFKFB3) is closely related to tumorigenesis and tumor development, and has important regulatory effects on the biological behavior of tumor cells. This study aimed to analyze the expression of PFKFB3 in gastric cancer and adjacent tissues, and to study its effect on the growth and apoptosis of gastric cancer cells and the underlying mechanism. Methods: TCGA database was used to analyze the expression of PFKFB3 in gastric cancer and adjacent tissues in 72 patients who received surgery at the Second Affiliated Hospital of Nanchang University and the Third Affiliated Hospital of Nanchang University, and the relationship between the expression of PFKFB3 and the prognosis of gastric cancer was further analyzed. Furthermore, the expression of PFKFB3 in gastric cancer tissue samples and their adjacent tissue samples was analyzed by real-time fluorescence quantitative polymerase chain reaction (FTFQ-PCR), Western blot and immunohistochemistry. Then, shNC and shPFKFB3 plasmids were transfected into gastric cancer cells, and the transfection efficiency was verified by RTFQ-PCR and Western blot. Cell counting kit-8 (CCK-8) and EdU experiments were used to analyze the proliferation of gastric cancer cells. Flow cytometry was used to detect cell cycle and apoptotic proportions after transfection of shNC and shPFKFB3 plasmids, and Western blot was used to analyze the proteins of cell cycle and apoptosis. Finally, we analyzed the mechanism of PFKFB3 affecting gastric cancer growth. Results: TCGA database analysis showed that the expression of PFKFB3 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.05), and the high expression of PFKFB3 was closely related to prognosis. In addition, RTFQ-PCR, Western blot and immunohistochemistry also confirmed that PFKFB3 was highly expressed in gastric cancer tissues (P<0.01), and high expression of PFKFB3 was significantly associated with lymph node metastasis and TNM stage (P<0.05). Silencing the expression of PFKFB3 in gastric cancer cells significantly inhibited cell proliferation (P<0.01), increased cell apoptotic rates (P<0.01) and induced G ₁ phase arrest (P<0.05). Mechanistically, PFKFB3 regulated the growth of gastric cancer cells by activating the phosphorylated PI3K/AKT signaling pathway. Conclusion: PFKFB3 is highly expressed in gastric cancer tissues and closely related to the prognosis of patients. Silencing the expression of PFKFB3 can inhibit the growth of gastric cancer and promote its apoptosis. PFKFB3 may be a potential biomarker for gastric cancer targeted therapy.

Key words: 6-phosphofructo-2-kinase 3, Gastric cancer, Growth, Apoptosis, Phosphoinositide 3-kinase/protein kinase