Insulin-like growth factor binding protein-3 (IGFBF-3) potentiates paclitaxel-induced apoptosis in human breast cancer cells

Variability in response to chemotherapy is poorly understood. Paclitaxel-in duced apoptosis was assessed in human Hs578T breast cancer cells, using the MTT assay, cell counting, morphological features and flow cytometry, Pre-d osing cells with non-glycosylated insulin-like growth factor binding protei n-3 (nglGFBP-3) had no effect on the cells per se but accentuated paclitaxe l-induced apoptosis, The apoptotic pathway was further examined by measurin g caspase-3 activity in cell lysates at time points over 48 hr after dosing with paclitaxel, Activity increased significantly, and Western immunoblots for caspase-3 in conditioned media showed that the inactive precursor decr eased after incubation with paclitaxel, Endogenous production of IGFBP-3 by the cells after incubation with paclitaxel was evaluated using Western lig and blotting, specific IGFBP-3 immunoblotting and radioimmunoassay. Paclita xel increased endogenous IGFBP-3, which was further increased if the cells had been pre-dosed with nglGFBP-3, These findings suggest that IGFBP-3 may be an important modulator of paclitaxel-induced apoptosis, Int. J, Cancer 8 8:448-453, 2000, (C) 2000 Wiley-Liss, Inc.