Synergistic Effect of Trifolium Pratense Extract and Temozolomide on Glioblastoma Multiforme Cell Line

Background: Glioblastoma multiforme (GBM) is the most malignantform of brain tumors and temozolomide (TMZ) is currentlypart of GBM standard treatment. Combination therapycan enhance the anti-cancer activity of TMZ. Trifolium pratenseL showed an anti-cancer potential on some cell lines. Theaim of the present study was to investigate the combination effectof T. pratense extract and TMZ on U۸۷MG cell line.Materials and Methods: The combination of TMZ and T.pratense extract was prepared in constant concentration ratio(۵.۵۷:۱) based on their corresponding IC۵۰ values in serial dilutionsabove and below the IC۵۰ value of each agent, and thenthe MTT assay was performed. The combination index (CI)and dose reduction index (DRI) were calculated using CompuSynsoftware (ComboSyn, Inc., Paramus, NJ, USA). The CIvalues were interpreted as additive (CI=۱), synergistic (CI<۱)and antagonistic (CI>۱). The DRI values represent the degree,to which the concentration of a compound can be reduced whenused in combination with another compound, to maintain anequivalent effect. Finally, Fa is the fraction of cell death rangingfrom ۰ (no cell killing) to ۱ (۱۰۰% cell killing).Results: Cell viability reduction by TMZ and T. pratense extractcombination was greater than either TMZ or T. pratenseextract alone. In addition, CI and DRI values were calculatedand showed that the CI values obtained in all tests were <۱,indicating a synergistic effect. The DRI values for TMZ were>۱ indicating a dose reduction for a given therapeutic effect.Conclusion: Combination of TMZ and T. pratense extract hada synergistic cytotoxic effect.

کلیدواژه ها:

Drug Combination ، Glioblastoma Multiforme ، Temozolomide