RESUMEN
OBJECTIVE: To explore the role of the P38 signaling pathway in the apoptosis of arsenic trioxide (As2 O3)-induced androgen-independent prostate cancer PC-3 cells. METHODS: Androgen-independent prostate cancer PC-3 cells were treated with different concentrations of As2 O3 for 24, 48 and 72 hours. The inhibitory effect of As2 O3 on the cell growth was measured by MTT, the expression of p- P38 detected by Western blot, and the rate of cell apoptosis determined by Annexin V and PI double staining before and after interfering the P38 signaling pathway by SB203580, a highly selective P38 inhibitor. RESULTS: As2 O3 inhibited the proliferation of PC-3 cells in a concentration- and time-dependent manner, and quickly activated P38 phosphorylation, thus giving full play to its biological activities. After 24 hours of treatment with As2 O3 at the concentrations of 2, 10 and 20 micromol/L, the apoptosis rates of the PC-3 cells were (18.9 +/- 0.43), (24.7 +/- 0.29) and (49.7 +/- 1.79)%, respectively, which were reduced to (14.8 +/- 0.81), (22.1 +/- 0.51) and (39.6 +/- 1.74)% after interfering the P38 pathway with SB203580. Inhibition of the P38 pathway significantly reduced the apoptosis of the PC-3 cells induced by As2 O3 (P < 0.05). CONCLUSION: As2 O3 can induce the apoptosis of prostate cancer PC-3 cells by activating the P38 signaling pathway, and interfering the P38 signaling pathway can reduce their apoptosis, which suggests that the P38 signaling pathway is involved in the apoptosis of As2 O3-induced androgen-independent prostate cancer PC-3 cells.
Asunto(s)
Arsenicales/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Óxidos/farmacología , Neoplasias de la Próstata/patología , Transducción de Señal/efectos de los fármacos , Trióxido de Arsénico , Línea Celular Tumoral , Humanos , Masculino , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoAsunto(s)
Disfunción Eréctil/complicaciones , Hiperprolactinemia/complicaciones , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológico , Adulto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Prolactinoma/complicacionesAsunto(s)
Disfunción Eréctil/tratamiento farmacológico , Testosterona/deficiencia , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Purinas/administración & dosificación , Citrato de Sildenafil , Sulfonas/administración & dosificación , Testosterona/administración & dosificación , Testosterona/análogos & derivadosRESUMEN
OBJECTIVE: Pituitary prolactinoma with severe erectile dysfunction (ED) as the initial symptom is often misdiagnosed. This article explores the diagnosis and treatment of severe ED caused by pituitary prolactinoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 4 cases of pituitary prolactinoma with severe ED (IIEF-5 score 5 - 7) as the initial clinical symptom confirmed by MRI. RESULTS: The 4 cases of pituitary prolactinoma-induced severe ED, with serum prolactin 10 times above the maximum normal level, were misdiagnosed for 2 years. All failed to respond to the PDE5 inhibitor therapy, and then 3 of them underwent transnasal hypophysectomy. Twenty-four months of follow-up found the level of prolactin restored to normal in 1 case (IIEF-5 = 19), and reduced to 600 and 768 IU/L respectively (IIEF-5 = 15) in the other 2. Then administration of the PDE5 inhibitor was followed, which produced satisfactory efficacy. One case was treated with oral bromocriptine, which restored the prolactin level to normal at 12 months (IIEF-5 > 21). CONCLUSION: Prolactin detection and brain MRI can help to confirm pituitary prolactinoma with severe ED at the onset. As for its treatment, in case of an extremely high level of prolactin, simple administration of the PDE5 inhibitor is ineffective. When the prolactin level is reduced after surgery or medication, the symptom of ED can be improved and, in case of no obvious relief, administration of the PDE5 inhibitor can be followed, which may achieve satisfactory results.