M2型丙酮酸激酶对膀胱癌细胞糖代谢及生长影响  

Effects of pyruvate kinase M2 on glucose metabolism and growth of bladder cancer cells

作　　者：杨杰[1] 吴国良 陈化磊[1] 蔡芳珍 何书明[1] YANG Jie;WU Guo-liang;CHEN Hua-lei;CAI Fang-zhen;HE Shu-ming(Department of Urology,The Second Affiliated Hospital of Hainan Medical College,Haikou 570100,China;Operating Room,The Second Affiliated Hospital of Hainan Medical College,Haikou 570100,China)

机构地区：[1]海南医学院第二附属医院泌尿外科,海南海口570100 [2]海南医学院第二附属医院手术室,海南海口570100

出　　处：《临床军医杂志》2024年第11期1160-1167,共8页Clinical Journal of Medical Officers

基　　金：海南省自然科学基金(820MS142);海南省自然科学基金高层次人才项目(820RC769);海南省自然科学基金项目(822QN472)。

摘　　要：目的探讨M2型丙酮酸激酶(PKM2)对膀胱癌细胞糖代谢及生长的影响。方法通过分析TCGA数据库中411例膀胱癌样本和19例癌旁样本评估PKM2在膀胱癌和癌旁组织中的表达及其预测价值;采用免疫组化、Western Blot、RT-qPCR检测PKM2表达,通过免疫组织芯片分析其在膀胱癌中的表达及其与预后的关系;构建si-PKM2低表达细胞模型,评估细胞增殖、迁移、侵袭、凋亡及糖代谢变化;通过慢病毒转染建立PKM2低表达稳转株并分析裸鼠模型中肿瘤的生长情况。结果PKM2在膀胱癌组织中表达升高,受试者工作特征曲线分析显示曲线下面积为0.718。免疫组化分析显示PKM2与肿瘤大小、分期、转移相关,高表达PKM2与较差预后相关。敲低PKM2后,细胞活力、克隆形成、迁移、侵袭能力降低,凋亡增加,糖代谢显著下降。PKM2低表达裸鼠肿瘤重量和乳酸含量减少。结论PKM2在膀胱癌组织中高表达,且与膀胱癌患者不良预后相关,抑制PKM2表达可降低膀胱癌细胞糖代谢能力,抑制癌细胞增殖、侵袭及迁移,并促进其凋亡。Objective To investigate the effects of pyruvate kinase M2(PKM2)on glucose metabolism and growth of bladder cancer cells.Methods The expression and predictive value of PKM2 in bladder cancer and paracancer tissues were evaluated by analyzing 411 bladder cancer samples and 19 paracancer samples in TCGA database.The expression of PKM2 was detected by immunohistochemistry,Western Blot and RT-qPCR.The expression of PKM2 in bladder cancer and its relationship with prognosis were analyzed by immunomicroarray.The cell model with low si-PKM2 expression was constructed to evaluate cell proliferation,migration,invasion,apoptosis and glucose metabolism.Lentivirus transfection was used to establish stable PKM2 strain with low expression and tumor growth was analyzed in nude mouse model.Results PKM2 expression was increased in bladder cancer tissues,and the area under the curve was 0.718.Immunohistochemical analysis showed that PKM2 was correlated with tumor size,stage and metastasis,and high expression of PKM2 was associated with poor prognosis.After PKM2 knockdown,cell viability,clone formation,migration and invasion ability decreased,apoptosis increased,glucose metabolism decreased significantly.The tumor weight and lactic acid content of nude mice with low PKM2 expression were decreased.Conclusion PKM2 is highly expressed in bladder cancer tissues and is associated with poor prognosis in patients with bladder cancer.Inhibition of PKM2 expression can reduce the glucose metabolism ability of bladder cancer cells,inhibit the proliferation,invasion and migration of cancer cells,and promote their apoptosis.

关 键 词：M2型丙酮酸激酶 膀胱癌 糖代谢 预后 

分 类 号：R737.14[医药卫生—肿瘤]