2. Academic Validation
  3. 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

  • Biomed Pharmacother. 2020 Jan;121:109521. doi: 10.1016/j.biopha.2019.109521.
Shangnan Dai 1,  Yunpeng Peng 1,  Yi Zhu 1,  Dalai Xu 1,  Feng Zhu 1,  Wenbin Xu 1,  Qiuyang Chen 1,  Xiaole Zhu 1,  Tongtai Liu 1,  Chaoqun Hou 1,  Junli Wu 2,  Yi Miao 3
Affiliations

Affiliations

  • 1 Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China; Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China.
  • 2 Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China; Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China. Electronic address: [email protected].
  • 3 Pancreas Center, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People's Republic of China; Pancreas Institute, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China. Electronic address: [email protected].
PMID: 31689601 DOI: 10.1016/j.biopha.2019.109521
Abstract

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.

Keywords

2-DG; Gemcitabine tolerance; Glycolysis; Pancreatic cancer; Prognostic model.

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