Effects of 2-Deoxy-glucose with Cisplatin-Pemetrexed in mesothelioma sphere formation.

Introduction: Glycolytic metabolism is enhanced in neoplasms, described as Warburg effect. Cisplatin (Cis) and Pemetrexed (Pem) are the only approved frontline therapies in malignant pleural mesothelioma (MPM). The exploitation of metabolic inhibition of glycolysis is not reported in mesothelioma studies. Aim: To examine the effects of 2-Deoxy-glucose (2DG) in combination with with Cis and Pem in reducing 3D tumor sphere formation in MPM cell lines. Methods: Three MPM cell lines were used in this study, M14K (epithelioid), MSTO (biphasic), ZL34 (sarcomatoid). Hanging drop method was used for tumor sphere formation (50 cells/drop) over 4 days [Controls (Con):10% FBS RPMI]. 2DG (2mM) alone and in combination with Cis 10μM or/and Pem 200μM was also used. Sphere sizes were measured by microscopic imaging for statistical analyses. Baseline perimeters were considered 100%. Results: 2DG significantly reduces sphere growth in MSTO (Con 100±2.7% vs. 2DG 85.11±1.8%; p Conclusions: In this preliminary work M14K sphere formation was unaffected by 2DG alone, while there was significantly reduced growth of MSTO, ZL34 spheres. In combination with Cis the spheres were smaller in all cell types, while in combination with Pem or Cis+Pem spheres were smaller only in MSTO and ZL34, but not in M14K.