TY - JOUR
T1 - SSRI use and clinical outcomes in epithelial ovarian cancer
AU - Christensen, Desiré K.
AU - Armaiz-Pena, Guillermo N.
AU - Ramirez, Edgardo
AU - Matsuo, Koji
AU - Zimmerman, Bridget
AU - Zand, Behrouz
AU - Shinn, Eileen
AU - Goodheart, Michael J.
AU - Bender, David
AU - Thaker, Premal H.
AU - Ahmed, Amina
AU - Penedo, Frank J.
AU - DeGeest, Koen
AU - Mendez, Luis
AU - Domann, Frederick
AU - Sood, Anil K.
AU - Lutgendorf, Susan K.
PY - 2016/5/31
Y1 - 2016/5/31
N2 - 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.
AB - 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.
KW - Cell proliferation
KW - Epithelial ovarian cancer
KW - Progression
KW - Selective serotonin reuptake inhibitors
KW - Serotonin
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U2 - 10.18632/oncotarget.8891
DO - 10.18632/oncotarget.8891
M3 - Article
C2 - 27121207
AN - SCOPUS:84973522306
SN - 1949-2553
VL - 7
SP - 33179
EP - 33191
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -