Investigation of the anti-cancer, anti-inflammatory and antiangiogenic effects of MTX-211 combination with a nonsteroidal anti-inflammatory drug

Glioblastoma multiforme is the most aggressive brain tumor where treatments fail due to tumor heterogeneity, difficulty in passing chemotherapeutics through the blood-brain barrier and rapid development of resistance to the drugs used in treatment. In our thesis study, we examined the cytotoxic effects of MTX-211, which inhibits EGFR and PI3Kinase, which are overexpressed in glioblastoma and diclofenac diethylamine, which inhibits COX-2/PGE2, which plays an important role in the development and progression of glioblastoma and the synergistic/antagonist effects of combined applications on THP-1, HUVEC and U87MG cells and apoptotic, anti-inflammatory, antimetastatic effects in U87MG and THP-1 co-culture and antiangiogenic effects in HUVEC and THP-1 co-culture were examined. While no significant cytotoxic effect was observed with MTX-211 and diclofenac diethylamine on the THP-1 cell line, it was determined that there were time- and concentration-dependent cytotoxic effects in the HUVEC cell line, strong cytotoxic effects occurred in the U87MG cell line and the combination application was synergistic in the U87MG cell line. Apoptosis was induced with MTX-211 and diclofenac diethylamine combinations, LPS-induced IL-1β, IL-6, IL-8, IL-10 and TNFα proinflammatory cytokine expressions were inhibited, U87MG and HUVEC cell migrations were strongly inhibited, resulting in strong antimetastatic and antiangiogenic effects occurred. As a result of experiments conducted using healthy cells and cancer cells, it was determined that MTX-211, a preclinical substance, diclofenac diethylamine, a nonsteroidal anti-inflammatory drug and their combinations had promising properties for cancer treatment. Keywords: MTX-211, Diclofenac, Glioblastoma, Anticancer