2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth

Anticancer Res. 2019 Jul;39(7):3809-3814. doi: 10.21873/anticanres.13530.


Background/aim: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy.

Materials and methods: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested.

Results: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types.

Conclusion: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.

Keywords: 2-deoxy-glucose; 2D cell cultures; 3D cell cultures; Warburg effect; cell proliferation; chemotherapy; malignant pleural mesothelioma.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Deoxyglucose / pharmacology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mesothelioma / drug therapy*
  • Mesothelioma, Malignant
  • Pemetrexed / pharmacology*
  • Pleural Neoplasms / drug therapy*
  • Spheroids, Cellular / drug effects*


  • Antineoplastic Agents
  • Pemetrexed
  • Deoxyglucose
  • Cisplatin