CBIO-19IBUPROFEN AND DICLOFENAC INHIBIT MIGRATION AND PROLIFERATION OF HUMAN GLIOMA CELL LINES IN VITRO

Abstract

Hallmarked by infiltrating tumor cells, GBM are characterized as highly malignant brain tumors. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been described to inhibit tumor cell proliferation as well as to induce tumor cell apoptosis in a Cox-independent way. The current study was designed to evaluate the effects of the NSAIDs diclofenac and ibuprofen - at concentrations routinely reached in patients who take these medications - on the proliferation, migration, and lactate formation in several human glioma cells. Significantly decreased migration and proliferation of GBM cells were observed from both diclofenac and ibuprofen treatment, whereas ASA had negligible effects. Additionally, diclofenac and ibuprofen affected cell proliferation, ibuprofen caused cell cycle arrest in G1, whereas cells treated with higher diclofenac concentrations arrested at the G2/M checkpoint. Both drugs lead to a decrease of lactate and pSTAT3 levels. To further investigate STAT3 effects, the specific inhibitor STATTIC, which prevents STAT3 phosphorylation, exhibited a comparable effect on cell proliferation and migration, supporting the substantial role of STAT3 in this regulation cascade. The in vitro results of this study indicate a potential advantage of diclofenac or to augment GBM treatment in patients, due to their migration and proliferation inhibiting effects. Further comparative studies with different NSAIDs and in vivo studies are necessary to affirm the positive effects of diclofenac and ibuprofen in glioma patient treatment.