Role of Dopamine as Antiangiogenic Agent in the Treatment of Prostate Cancer; Annual rept. 15 Jan 2007-14 Jan 2008

摘要

Prostate cancer is a major cause of cancer-related mortality for men in the United States. The established treatment protocol for the advanced stage of the disease is by surgical castration and or chemotherapy. Although androgen ablation therapy is initially effective in inhibiting tumor growth in most patients, however with time, the tumors recurs with a more aggressive and metastatic phenotype, ultimately causing death. Thus limitation of treatment underscores the need of development of an alternative treatment approach. Several reports suggest that vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) induced angiogenesis is essential for the growth and metastasis of prostate cancer. As our recent reports indicate that the neurotransmitter dopamine (DA) can specifically and significantly inhibit VPF/VEGF induced angiogenesis, therefore, we investigated whether DA can inhibit angiogenesis, and thereby growth of prostate cancer. We here in this report demonstrate that DA can significantly inhibit PC3 human prostate cancer growth by inhibiting VPF/VEGF mediated angiogenesis by suppressing VEGFR-2 phosphorylation in tumor endothelial cells. Thus our results are significant because DA is already in clinical use with an established safety record; therefore our study may be rapidly translated to the clinics as a new and more effective therapy for prostate cancer.