RESUMO
Purpose: To conduct a population-based study to determine whether the use of GnRH agonist and antiandrogens are associated with an increased risk of cardio-cerebrovascular disease (CCVD) in Asian patients with prostate cancer using the National Health Insurance Service-Elderly Cohort Database (NHIS-ECD). Materials and Methods: We included a total of 2,413 men aged 60 years or older with prostate cancer between January 2003 and December 2008. Outcomes of interest included the first occurrence of cardiovascular events [acute myocardial infarction (AMI), ischemic heart disease (IHD)] and cerebrovascular events [ischemic stroke (IS), and cerebrovascular disease (CVD)]. Results: The 5-year AMI-free rates of patients diagnosed with prostate cancer and treated with GnRH agonists, antiandrogens alone, or androgen deprivation therapy (ADT)-naïve interventions were 97.0%, 96.5%, and 98.3%, respectively, while the 5-year IHD-free rates were 93.2%, 92.3%, and 94.5%, respectively. Exposure to GnRH agonists or antiandrogen regimens did not significantly increase the risk of AMI or IHD compared to ADT-naïve treatment in multivariate Cox proportional-hazards models after adjusting for other covariates. Five-year IS-free rates of patients exposed to GnRH agonists, antiandrogens alone, and those with ADT-naïve prostate cancer were 94.8%, 94.7%, and 95.5%, respectively, while the five-year CVD-free rates were 92.9%, 93.3%, and 94.6%, respectively. Cox proportional-hazards models also failed to show that men who received GnRH agonist or antiandrogen treatment alone carried a significantly increased risk for IS or CVD compared to ADT-naïve patients. Conclusions: The current study based on Asian population suggests that treatment with neither GnRH agonist nor antiandrogens increases the risk of cardio-cerebrovascular disease compared to patients with ADT-naïve prostate cancer.
RESUMO
Purpose: We examined the effect of GV1001 in castration castration-resistant prostate cancer (CRPC) cell growth and invasion and explored the potential molecular mechanisms of action. Materials and Methods: The in vitro anti-cancer effects of GV1001 in CRPC cells were examined using cell viability assay, TUNEL assay, and flow cytometry analysis. To evaluate the effects of GV1001 on different steps of angiogenesis, wound healing assay, transwell invasion assay, endothelial cell tube formation assay, and western blot analysis were performed. Finally, the anti-cancer effects of GV1001 on tumor growth in vivo were examined in a CRPC xenograft model. Results: GV1001 inhibited cell viability and induced apoptosis in CRPC cells in vitro, accompanied by down-regulation of Bcl-2 and caspase-3. GV1001 also inhibited different steps of angiogenesis, such as migration, invasion, and endothelial tube formation, along with decreased expression of MMP-2, MMP-9, and CD31 and increased expression of TIMP-1 and TIMP-2. Mechanistically, GV1001 significantly decreased the levels of phosphorylated AKT, phosphorylated p65, and VEGF in CRPC cells in a dose-dependent manner. GV1001 was effective in suppressing tumor growth and inducing apoptosis in a CRPC xenograft mouse model. Conclusions: Our data demonstrated that GV1001 inhibited cell viability, induced apoptosis, and inhibited angiogenesis in CRPC cells by inhibition of the AKT/NF-κB/VEGF signaling pathway.
