RESUMO
Prostate cancer is one of the most prevalent tumors. The switch of androgen signal dependence makes therapy more complex. Although reports on introduction of a single suicide gene exist, double suicide gene therapy has not been reported yet. In the current study, two suicide genes were constructed in the pIRES plasmid driven by PSMA promoter. 5-FC and GCV combination in vitro led to a higher growth inhibition on prostate cancer compared to a single pro-drug. Retarded xenograft tumor growth was observed in castrated nude mice after double suicide gene activation. Furthermore, decreased metastasis was observed with double suicide gene treatment. These findings suggest that specific double suicide gene strategy could be a potential option for the therapy of prostate cancer.
Assuntos
Genes Transgênicos Suicidas/genética , Terapia Genética/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Simplexvirus/genética , Timidina Quinase/genética , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Masculino , Modelos Genéticos , Metástase Neoplásica , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the effect of nitric oxide (NO) on human sperm capacitation and acrosome reaction (AR). METHODS: Different concentrations of sodium nitroprusside (SNP) were added to the sperm suspension from 48 healthy fertile men, and the suspension was incubated in 1 x Earle at 37 degrees C for 1 hour. Progesterone was used to induce AR for 15, 30, 45 and 60 min, and then acid phosphatase (ACP) activity in the suspension before and after capacitation and at different time of AR was measured by p-nitrophenyl sodium phosphate assay. In the meantime, sperm motile parameters were assayed by CASA to observe sperm capacitation and AR. RESULTS: ACP activity and sperm motile parameters increased in the 50 approximately 100 nmol/L NO concentration group, showed no significant variation in the 150 approximately 200 nmol/L group, and decreased in the 250 approximately 300 nmol/L group. CONCLUSION: NO can facilitate sperm capacitation, AR and sperm motile parameters in low concentration and suppress them in high concentration. ACP activity assay of sperm is an objective and reliable method to evaluate sperm capacitation and AR in whole sperm population.
