Effect of VEGFR, PDGFR and PI3K/mTOR Targeting in Glioblastoma.

Resistance to targeted therapy is a well known obstacle in cancer therapy. The cross-talk between several growth factor receptors generates redundancy in their intracellular pathways that usually mediates resistance to receptor targeted therapy. Simultaneous inactivation of two or more growth factor receptors has been suggested to prevent the cross-talk between their signaling pathways and to better eliminate malignant cells. Here we found that targeted therapy against these receptors induced moderate cell death in glioblastoma cells. More important, dual PDGFR and VEGFR inactivation induced more pronounceable cell death compared to inactivation of each receptor alone but failed to induce synergistic cell death in glioblastoma. PI3K/mTOR dual targeting has been identified as an efficient therapeutic approach in several malignant diseases, including glioblastoma. Therefore, we also investigated the PI3K/mTOR pathways inhibition effect in glioblastoma cells. Our results showed that inactivation of PI3K/mTOR pathways were more efficient than PDGFR or VEGFR single targeting or their dual inhibition.

The Effect of Human Mesenchymal Stem Cells-Conditioned Media on Glioblastoma Cells Viability In Vitro.

A novel target for cancer treatment is based on the effects of non-tumor cells, including hMSCs on tumor growth. However, the results are controversial: some studies showed that hMSCs inhibit tumor progression, while others found they promote tumor cell proliferation. In this study, we analyse the effect of human mesenchymal cells derived from umbilical cord tissue (hUC-MSCs) and bone-marrow- mesenchymal stem cells (hBM-MSCs) on glioblastoma cells viability in vitro. GB cell cultures were established from fresh sample tissues provided by "Bagdasar-Arseni" Hospital, Bucharest, from consented GB patients. hUC-MSCs, HUC-1 and HUC-2 cell lines, were established from human umbilical cord tissue collected after delivery from natural term births at the Emergency Hospital of Craiova, Romania. hBM-MSCs cell line was purchased from Life Technologies. Conditioned media (CM) from MSCs was used to treat GB cells for 24, 48, 72 and 96 hours. To determine GB cell viability was used MTT cell proliferation assay. Statistical analyses were performed using Students t-test. hUC-MSCs CM displayed the potential to be cytotoxic to GB cells, while the treatment with hBM-MSCs CM significantly stimulated GB cell growth 24 hours after the treatment and showed minor growth cell inhibition 48, 72 and 96 hours after the treatment. This report proved that hUC-MSCsCM inhibited GB cell proliferation, while little inhibitory effect was exerted by hBM-MSCs CM.