A study on the expression of PFKFB3 in gastric cancer and its effect on the growth and apoptosis of gastric cancer cells

刘　鹏; 龚　阳; 刘道江; 张　翔; 张佳楠; 杨高亮; 方　念

doi:10.19401/j.cnki.1007-3639.2020.04.005

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A study on the expression of PFKFB3 in gastric cancer and its effect on the growth and apoptosis of gastric cancer cells

更新时间：2026-01-27

- A study on the expression of PFKFB3 in gastric cancer and its effect on the growth and apoptosis of gastric cancer cells
- China Oncology Vol. 30, Issue 4, Pages: 268-274(2020)
- 作者机构：
  
  1. 南昌大学第三附属医院消化内科,江西,南昌,330008
  2. 新余市人民医院普外科,江西,新余,338025
  3. 阳新县人民医院消化内科,湖北,黄石,435200
  4. 南昌大学第二附属医院病理科,江西,南昌,330008
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2020.04.005
  CLC： R735.2
- Published Online：12 May 2020，
  
  Published：12 May 2020
- 稿件说明：
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刘　鹏 , 龚　阳 , 刘道江 , 张　翔 , 张佳楠 , 杨高亮 , 方　念 . PFKFB3在胃癌中的表达及对胃癌细胞生长和凋亡的影响研究[J]. 中国癌症杂志, 2020, 30(4): 268-274.

刘　鹏, 龚　阳, 刘道江, et al. A study on the expression of PFKFB3 in gastric cancer and its effect on the growth and apoptosis of gastric cancer cells[J]. China Oncology, 2020, 30(4): 268-274.
刘　鹏 , 龚　阳 , 刘道江 , 张　翔 , 张佳楠 , 杨高亮 , 方　念 . PFKFB3在胃癌中的表达及对胃癌细胞生长和凋亡的影响研究[J]. 中国癌症杂志, 2020, 30(4): 268-274. DOI： 10.19401/j.cnki.1007-3639.2020.04.005.

刘　鹏, 龚　阳, 刘道江, et al. A study on the expression of PFKFB3 in gastric cancer and its effect on the growth and apoptosis of gastric cancer cells[J]. China Oncology, 2020, 30(4): 268-274. DOI： 10.19401/j.cnki.1007-3639.2020.04.005.

摘要

背景与目的：6-磷酸果糖激酶-2同工酶3（6-phosphofructo-2-kinase 3，PFKFB3）与肿瘤的发生、发展密切相关，且对肿瘤细胞的生物学行为具有重要的调节作用。分析PFKFB3在胃癌组织及癌旁组织中的表达，并观察其对胃癌细胞生长和凋亡的作用及机制。方法：采用TCGA数据库分析72例在南昌大学第二附属医院及第三附属医院经外科手术切除的新鲜胃癌标本及其相应的癌旁组织中PFKFB3的表达，并分析PFKFB3的表达与胃癌预后的关系。进一步通过实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）、蛋白质印迹法（Western blot）及免疫组织化学法分析胃癌组织标本及癌旁组织标本中PFKFB3的表达。shNC及shPFKFB3质粒转染至胃癌细胞中，采用RTFQ-PCR和Western blot验证转染效率。分别通过细胞计数试剂盒-8（cell counting kit-8，CCK-8）实验、EdU实验、流式细胞术和Western blot分析PFKFB3下调后对胃癌细胞的增殖能力、细胞周期变化和细胞凋亡的影响。最后采用Western blot分析PFKFB3影响胃癌细胞生长的机制。结果：TCGA数据库分析显示，胃癌组织中PFKFB3的表达明显高于癌旁组织（P＜0.05），且PFKFB3高表达与胃癌患者较差的预后密切相关。另外，RTFQ-PCR、Western blot及免疫组织化学检测也同样证实PFKFB3在胃癌组织中高表达（P＜0.01），且PFKFB3的表达升高与淋巴结转移及TNM分期密切相关（P＜0.05）。沉默胃癌细胞中PFKFB3的表达后，其生长能力明显减弱（P＜0.01），胃癌细胞凋亡比例增加（P＜0.01），细胞周期G

期阻滞（P＜0.01）。PFKFB3通过激活磷酸化磷脂酰肌醇3-激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）信号通路而调控胃癌细胞的生长。结论：PFKFB3在胃癌组织中高表达，且与患者预后密切相关，沉默PFKFB3的表达后抑制胃癌细胞的生长并促进其凋亡，PFKFB3可能是胃癌靶向治疗的潜在生物标志物。

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 (P0.05)

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 (P0.01)

and high expression of PFKFB3 was significantly associated with lymph node metastasis

and TNM stage (P0.05). Silencing the expression of PFKFB3 in gastric cancer cells significantly inhibited cell proliferation (P0.01)

increased cell apoptotic rates (P0.01) and induced G

phase arrest (P0.05). 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.

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