Li Wenfeng, Xu Zhengyang, Hong Junfeng, Xu Yunsheng
Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, Zhejiang, China,
Med Oncol. 2014 Sep;31(9):118. doi: 10.1007/s12032-014-0118-1. Epub 2014 Jul 27.
Enhanced glycolysis is a common trait of many types of human cancers. This study was to detect the expression pattern of three regulatory enzymes during glycolysis in esophageal squamous cell carcinoma (ESCC) and to investigate their correlation with patients' outcome based on banked pathology material. A total of 141 surgically resected specimens of primary ESCC patients without prior treatments were retrospectively recruited from the First Affiliated Hospital of Wenzhou Medical College Hospital from 2007 to 2009. Expression of HK1, PFKB, and PKM2 in ESCC specimens was analyzed by immunohistochemical staining and Western blotting analysis. HK1-shRNA was used to knock down HK1 expression in ESCC cells, and the functional significance was assessed by CCK8 assay. It was found that the expression of two glycolytic enzymes, HK1 and PKM2, was associated with disease progression, invasion, and poor survival of patients with ESCC. Silence of HK1-inhibited cell proliferation in vitro and suppressed phospho-S6 kinase expression. Our findings suggest that activation of key enzymes in glycolysis might serve as potential therapeutic targets and/or prognostic factors for patients with ESCC.
糖酵解增强是多种人类癌症的共同特征。本研究旨在检测食管鳞状细胞癌(ESCC)糖酵解过程中三种调节酶的表达模式,并基于存档的病理材料研究它们与患者预后的相关性。2007年至2009年,从温州医科大学附属第一医院回顾性招募了141例未经治疗的原发性ESCC患者的手术切除标本。通过免疫组织化学染色和蛋白质印迹分析检测ESCC标本中HK1、PFKB和PKM2的表达。使用HK1-shRNA敲低ESCC细胞中HK1的表达,并通过CCK8测定评估其功能意义。发现两种糖酵解酶HK1和PKM2的表达与ESCC患者的疾病进展、侵袭和不良生存相关。HK1沉默抑制体外细胞增殖并抑制磷酸化S6激酶表达。我们的研究结果表明,糖酵解关键酶的激活可能作为ESCC患者的潜在治疗靶点和/或预后因素。