SSRI use and clinical outcomes in epithelial ovarian cancer

Desiré K Christensen; Guillermo N Armaiz-Pena; Edgardo Ramirez; Koji Matsuo; Bridget Zimmerman; Behrouz Zand; Eileen Shinn; Michael J Goodheart; David Bender; Premal H Thaker; Amina Ahmed; Frank J Penedo; Koen DeGeest; Luis Mendez; Frederick Domann; Anil K Sood; Susan K Lutgendorf

doi:10.18632/oncotarget.8891

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SSRI use and clinical outcomes in epithelial ovarian cancer

Journal article

Open access

Peer reviewed

SSRI use and clinical outcomes in epithelial ovarian cancer

Desiré K Christensen, Guillermo N Armaiz-Pena, Edgardo Ramirez, Koji Matsuo, Bridget Zimmerman, Behrouz Zand, Eileen Shinn, Michael J Goodheart, David Bender, Premal H Thaker, …

Oncotarget, Vol.7(22), pp.33179-33191

05/31/2016

DOI: 10.18632/oncotarget.8891

PMCID: PMC5078084

PMID: 27121207

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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.

Antidepressive Agents, Second-Generation - adverse effects

Multivariate Analysis

Up-Regulation

Receptor, Serotonin, 5-HT2A - genetics

United States

Humans

Middle Aged

Gene Expression Regulation, Neoplastic

Ovarian Neoplasms - pathology

Neoplasms, Glandular and Epithelial - metabolism

Tumor Microenvironment

Ki-67 Antigen - metabolism

Sertraline - adverse effects

Ovarian Neoplasms - mortality

Neoplasms, Glandular and Epithelial - mortality

Time Factors

Aged, 80 and over

Adult

Ovarian Neoplasms - metabolism

Odds Ratio

Neoplasms, Glandular and Epithelial - pathology

Risk Assessment

Risk Factors

Kaplan-Meier Estimate

Neoplasm Recurrence, Local

Neoplasms, Glandular and Epithelial - therapy

Proportional Hazards Models

Serotonin Uptake Inhibitors - adverse effects

Chi-Square Distribution

Xenograft Model Antitumor Assays

Animals

Mice, Nude

Serotonin - metabolism

Carcinoma, Ovarian Epithelial

Cell Line, Tumor

Ovarian Neoplasms - therapy

Aged

Receptor, Serotonin, 5-HT2A - metabolism

Details

Title: Subtitle: SSRI use and clinical outcomes in epithelial ovarian cancer
Creators: Desiré K Christensen - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa, USA
Guillermo N Armaiz-Pena - Department of Pharmacology, Ponce Health Sciences University, Ponce, Puerto Rico
Edgardo Ramirez - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa, USA
Koji Matsuo - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA
Bridget Zimmerman - Department of Biostatistics, University of Iowa, Iowa City, Iowa, USA
Behrouz Zand - Department of Cancer Biology, and Center for RNA Interference and Noncoding RNA, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA
Eileen Shinn - Department of Behavioral Science, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA
Michael J Goodheart - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA
David Bender - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa, USA
Premal H Thaker - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA
Amina Ahmed - Department of Obstetrics and Gynecology, Lutheran General Hospital, Park Ridge, Illinois, USA
Frank J Penedo - Department of Medical Social Sciences, Northwestern University, Chicago, Illinois, USA
Koen DeGeest - Division of Gynecologic Oncology, Oregon Health and Sciences University, Portland, Oregon, USA
Luis Mendez - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Florida International University School of Medicine, Miami, Florida, USA
Frederick Domann - Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA
Anil K Sood - Department of Cancer Biology, and Center for RNA Interference and Noncoding RNA, UT MD Anderson Comprehensive Cancer Center, Houston, Texas, USA
Susan K Lutgendorf - Department of Urology, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(22), pp.33179-33191
DOI: 10.18632/oncotarget.8891
PMID: 27121207
PMCID: PMC5078084
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: United States
Grant note: R01 CA140933 / NCI NIH HHS R21 CA088293 / NCI NIH HHS R01 CA104825 / NCI NIH HHS P30 CA016672 / NCI NIH HHS P50 CA083639 / NCI NIH HHS R01 CA193249 / NCI NIH HHS R01 CA109298 / NCI NIH HHS P30 CA060553 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA116778 / NCI NIH HHS
Language: English
Date published: 05/31/2016
Academic Unit: Psychological and Brain Sciences; Pathology; Iowa Neuroscience Institute; Biostatistics; Surgery; Radiation Oncology; Obstetrics and Gynecology; Urology
Record Identifier: 9983931505202771

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