2-Deoxy-glucose synergizes with Cisplatin and Pemetrexed chemotherapeutics to reduce cell migration of mesothelioma cells

Abstract

Introduction: Metabolic adaptations favor survival of cancer cells with higher glucose uptake. 2-Deoxy-glucose (2DG), a mimetic of glucose cannot undergo further glycolysis and hampers cell growth, essential during tumor metabolism. Chemotherapy with Cisplatin (Cis) and Pemetrexed (Pem) is the main treatment for malignant pleural mesothelioma (MPM). However, there is lack of evidence on the effects of 2DG in MPM. Aim: To assess the synergistic effect of 2DG with Cis+Pem during cell migration in wound scratch assay. Methods: Epithelioid (M14K), biphasic (MSTO) and sarcomatoid (ZL34) MPM cells were used in the study. Cells were grown into confluent monolayers and wounded. Wound widths were measured by microscopic imaging immediately and 8 hours after wound scratch in 10%FBS-RPMI (con), Cis(10μM)+Pem(200μM) or 2DG(3mM)+Cis+Pem. Statistical analyses were performed to assess cell migration. Results: Migration with both treatments (Cis+Pem, 2DG+Cis+Pem) was significantly reduced compared to controls in all cell lines (M14K: con: 0.33±0.02, Cis+Pem: 0.16±0.01, p Conclusions: Combined 2DG and Cis+Pem reduce migration of MPM cells, but the addition of 2DG does not improve further the efficacy of first line chemotherapeutics in inhibiting cell migration rate.