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Oncotarget. 2016 May 31;7(22):33179-91. doi: 10.18632/oncotarget.8891.

SSRI use and clinical outcomes in epithelial ovarian cancer.

Author information

1
Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa, USA.
2
Department of Pharmacology, Ponce Health Sciences University, Ponce, Puerto Rico.
3
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA.
4
Department of Biostatistics, University of Iowa, Iowa City, Iowa, USA.
5
Department of Gynecologic Oncology and Reproductive Medicine, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA.
6
Department of Cancer Biology, and Center for RNA Interference and Noncoding RNA, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA.
7
Department of Behavioral Science, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA.
8
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, USA.
9
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA.
10
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA.
11
Department of Obstetrics and Gynecology, Lutheran General Hospital, Park Ridge, Illinois, USA.
12
Department of Medical Social Sciences, Northwestern University, Chicago, Illinois, USA.
13
Division of Gynecologic Oncology, Oregon Health and Sciences University, Portland, Oregon, USA.
14
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Florida International University School of Medicine, Miami, Florida, USA.
15
Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA.
16
Department of Urology, University of Iowa, Iowa City, Iowa, USA.

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.

KEYWORDS:

cell proliferation; epithelial ovarian cancer; progression; selective serotonin reuptake inhibitors; serotonin

PMID:
27121207
PMCID:
PMC5078084
DOI:
10.18632/oncotarget.8891
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

All authors listed above certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest in the subject matter discussed in this manuscript.

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