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Background: Conjugated linoleic acid (CLA) has strong chemoprotective properties in experimental animal models. The insulin-like growth factor (IGF) system has been implicated as a risk factor for the development of bladder cancer. The present study examined CLA regulation of TSU-Pr1 bladder cancer cell proliferation and apoptosis and the influence of CLA on IGF-I receptor (IGF-IR) signaling., Materials and Methods: TSU-Pr1 cells were cultured in serum-free medium with 0, 2, 5, or 10 microM CLA and/or 10 nM IGF-I. [3H]Thymidne incorporation, DNA laddering, FACS analysis, immunoprecipitation and Western blotting were performed., Results: CLA decreased DNA synthesis and induced apoptosis in TSU-Pr1 cells dose-dependently. Exogenous IGF-I alone increased viable cell numbers but did not counteract growth inhibition induced by CLA. CLA decreased IGF-IR and insulin receptor substrate (IRS)-1 protein levels. In addition, CLA decreased IGF-I-induced phosphorylation of IGF-IR and IRS-1, recruitment of the p85 subunit of phosphoinositide 3-kinase to IRS-1 and phosphorylation of Akt and extracellular signal-regulated kinase-1/2., Conclusion: These results suggest that CLA inhibits cell proliferation and stimulates apoptosis of TSU-Pr1 cells via its inhibition of the IGF-IR signaling pathway.