The median effect analysis originally proposed by Chou and Talalay [57,58] was employed to determine the nature (synergism, additivity and antagonism) of drugs and drug interactions. Cells were treated with serial dilutions of each drug alone or with drug combinations at fixed ratios based on their corresponding IC50 values. The computed parameter, termed the combination index (CI), allows the quantitative determination of drug interactions at increasing levels of cell killing by classifying the tumoricidal activity as additive (CI value 1.0), synergistic (CI < 1.0), or antagonistic (CI > 1.0).
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