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

✍ Scribed by C.A. Fowler; C.M. Perks; P.V. Newcomb; P.B. Savage; J.R. Farndon; J.M.P. Holly

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 145 KB
• Volume: 88
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/1097-0215(20001101)88:3<448::aid-ijc18>3.0.co;2-v

✦ Synopsis

Variability in response to chemotherapy is poorly understood. Paclitaxel-induced apoptosis was assessed in human Hs578T breast cancer cells, using the MTT assay, cell counting, morphological features and flow cytometry. Pre-dosing cells with non-glycosylated insulin-like growth factor binding protein-3 (ngIGFBP-3) had no effect on the cells per se but accentuated paclitaxel-induced apoptosis. The apoptotic pathway was further examined by measuring 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 decreased after incubation with paclitaxel. Endogenous production of IGFBP-3 by the cells after incubation with paclitaxel was evaluated using Western ligand blotting, specific IGFBP-3 immunoblotting and radioimmunoassay. Paclitaxel increased endogenous IGFBP-3, which was further increased if the cells had been pre-dosed with ngIGFBP-3. These findings suggest that IGFBP-3 may be an important modulator of paclitaxel-induced apoptosis. Int.