Oncotarget, Vol. 7, No. 22
www.impactjournals.com/oncotarget/
SSRI use and clinical outcomes in epithelial ovarian cancer Desiré K. Christensen1, Guillermo N. Armaiz-Pena2, Edgardo Ramirez1, Koji Matsuo3, Bridget Zimmerman4, Behrouz Zand5,6, Eileen Shinn7, Michael J. Goodheart8,9, David Bender8, Premal H. Thaker10, Amina Ahmed11, Frank J. Penedo12, Koen DeGeest13, Luis Mendez14, Frederick Domann15, Anil K. Sood5,6, Susan K. Lutgendorf1,8,9,16 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
epartment of Cancer Biology, and Center for RNA Interference and Noncoding RNA, UT MD Anderson Comprehensive D 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
ivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Florida International University School of D 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
Correspondence to: Susan K. Lutgendorf, e-mail: [email protected] Keywords: selective serotonin reuptake inhibitors, epithelial ovarian cancer, serotonin, progression, cell proliferation Received: November 09, 2015 Accepted: April 02, 2016 Published: April 21, 2016
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
www.impactjournals.com/oncotarget/
SSRI use and clinical outcomes in epithelial ovarian cancer Desiré K. Christensen1, Guillermo N. Armaiz-Pena2, Edgardo Ramirez1, Koji Matsuo3, Bridget Zimmerman4, Behrouz Zand5,6, Eileen Shinn7, Michael J. Goodheart8,9, David Bender8, Premal H. Thaker10, Amina Ahmed11, Frank J. Penedo12, Koen DeGeest13, Luis Mendez14, Frederick Domann15, Anil K. Sood5,6, Susan K. Lutgendorf1,8,9,16 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
epartment of Cancer Biology, and Center for RNA Interference and Noncoding RNA, UT MD Anderson Comprehensive D 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
ivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Florida International University School of D 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
Correspondence to: Susan K. Lutgendorf, e-mail: [email protected] Keywords: selective serotonin reuptake inhibitors, epithelial ovarian cancer, serotonin, progression, cell proliferation Received: November 09, 2015 Accepted: April 02, 2016 Published: April 21, 2016
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
