Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine
Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine
复制标题
糖酵解促进胰腺癌的进展并降低癌细胞对吉西他滨的敏感性
DOI：
10.1016/j.biopha.2019.109521
复制
发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Miao, Yi
中科院分区：
文献类型：
--
作者：
Dai, Shangnan;Peng, Yunpeng;Miao, Yi
先前的研究报道了糖酵解活性的增加会增强某些类型恶性肿瘤的化疗耐药性。然而，糖酵解是否会影响吉西他滨（GEM）对胰腺癌（PC）细胞的疗效尚不清楚。本研究的目的是研究PC中糖酵解的状态及其与GEM耐受性的关系。利用肿瘤基因组图谱（TCGA）的数据分析糖酵解相关基因（GRG）表达与PC进展和预后的相关性。应用2-脱氧- d -葡萄糖（2-DG）来评估糖酵解抑制对PC细胞死亡和GEM耐受性的影响。一些GRGs如HK1、GAPDH、PKM2、LDHA的表达与PC的预后有显著相关性。此外，HK1、PKLR和LDHA的表达与PC的进展呈正相关。进一步的分析表明，糖酵解抑制显著增强了癌细胞的死亡，并且在2-DG的存在下，癌细胞对GEM的敏感性显著增加。我们的研究结果表明，异常升高的糖酵解活性促进了PC的发展，并增强了对GEM的耐受性。2-DG联合GEM是治疗PC的潜在疗法。
Previous studies have reported that increased glycolytic activity enhances chemotherapy resistance in some types of malignancies. However, whether glycolysis influences the curative effect of gemcitabine (GEM) on pancreatic cancer (PC) cells remains unclear. The aim of this study was to investigate the status of glycolysis in PC and its association with tolerance to GEM. Data from The Cancer Genome Atlas (TCGA) were used to analyze the correlation between glycolysis-related gene (GRG) expression and PC progression and prognosis. 2-Deoxy-D-glucose (2-DG) was applied to assess the effect of glycolysis inhibition on PC cell death and GEM tolerance. Expression of some GRGs, such as HK1, GAPDH, PKM2, and LDHA, was significantly associated with the prognosis of PC. Furthermore, HK1, PKLR, and LDHA expression correlated positively with PC progression. Further analysis revealed that cancer cell death was markedly enhanced following glycolysis inhibition and that the sensitivity of cancer cells to GEM was notably increased in the presence of 2-DG. Our findings indicate that abnormally increased glycolytic activity promotes the development of PC and enhances drug tolerance to GEM. 2-DG combined with GEM is a potential therapy for PC.