SSRI use and clinical outcomes in epithelial ovarian cancer.
Oncotarget
; 7(22): 33179-91, 2016 May 31.
Article
en En
| MEDLINE
| ID: mdl-27121207
ABSTRACT
Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Serotonina
/
Inhibidores Selectivos de la Recaptación de Serotonina
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Neoplasias Glandulares y Epiteliales
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Antidepresivos de Segunda Generación
/
Sertralina
/
Microambiente Tumoral
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged80
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Oncotarget
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos