The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer
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Anuj Suri1, Xiugui Sheng2,*, Kevin M. Schuler3, Yan Zhong4,5, Xiaoyun Han2,4, Hannah M. Jones4, Paola A. Gehrig4,6, Chunxiao Zhou4,6, Victoria L. Bae-Jump4,6
1Houston Methodist Gynecologic Oncology Associates, Houston, TX, USA
2Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan University, Jinan, Shandong, China
3Good Samaritan Hospital, Division of Gynecologic Oncology, Cincinnati, OH, USA
4Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
5Department of Gynecologic Oncology, Linyi Cancer Hospital, Shandong, China
6Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
*This author contributed an equal amount of work as the first author
Victoria L. Bae-Jump, e-mail: firstname.lastname@example.org
Chunxiao Zhou, e-mail: email@example.com
Keywords: ovarian cancer, COX-2 inhibitor, celecoxib, obesity, genetically engineered mouse model
Received: January 21, 2016 Accepted: March 28, 2016 Published: April 8, 2016
Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.
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