Improved Antiproliferative Effect of Cisplatin Combined with Phorbol Ester

Abstract

A combination of cisplatin (DDP) and tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or nonphorboid tumor promoter mezerein (MEZ) were tested by 5-bromo-deoxyuridine (BrdU) and 3,4,5-dimeth-ylthiazol-2,5-disphenyl-tetrazolium bromide (MTT) assays for their antiproliferative actions. DDP and TPA showed a synergistic effect at concentrations where the single drug did not show any significant action. The BrdU assay seemed to be more sensitive than the MTT assay in measuring these drug effects. Epidermal growth factor (EGF)-receptor number and affinity on treated cells were not altered as showed by ¹²⁵I-EGF-receptor assay. EGF stimulation experiments suggested an inhibition of receptor-mediated signal transduction by TPA.