Temozolomide and tranilast synergistic antiproliferative effect on human glioblastoma multiforme cell line (U87MG)

Abstract

Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Temozolomide (TMZ) is a chemotherapeutic agent that has been used in GBM treatment. Resistance to TMZ is a major obstacle to successful GBM treatment. The aim of the present study was to investigate the effect of TMZ and tranilast on human GBM cell line (U87MG). Methods: In this in vitro experimental study, the effect of TMZ and tranilast on cell proliferation was measured using the MTT assay. Median effect analysis was performed to determine the TMZ and tranilast interaction. Lactate dehydrogenase assay was used to determine TMZ and tranilast cytotoxicity. Cell fluorescent staining and real-time PCR were used for apoptosis evaluation. The effect of TMZ and tranilast on U87MG nitric oxide (NO) production was evaluated by Griess assay. Results: TMZ and tranilast had a significant dose- and time-dependent inhibitory effect on cell proliferation. The mean combination index values represented a synergistic effect, and dose reduction index values suggested the advantages of reducing the toxicity, adverse effects, and drug resistance in combination of TMZ and tranilast. Apoptosis cell death was induced by TMZ and/or tranilast in cells. TMZ and tranilast reduced NO. production in cells. Conclusion: TMZ and tranilast combination inhibited the GBM cells growth effectively.