title: The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.
abstract: 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.
authors.affiliation: Houston Methodist Gynecologic Oncology Associates, Houston, TX, USA.
authors.forename: Anuj
authors.initials: A
authors.lastname: Suri
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan University, Jinan, Shandong, China.
authors.forename: Xiugui
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Good Samaritan Hospital, Division of Gynecologic Oncology, Cincinnati, OH, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Schuler
authors.affiliation: Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Gynecologic Oncology, Linyi Cancer Hospital, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan University, Jinan, Shandong, China.|Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Han
authors.affiliation: Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jones
authors.affiliation: Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Paola A
authors.initials: PA
authors.lastname: Gehrig
authors.affiliation: Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
mesh_terms: D000818:Animals; D017209:Apoptosis; D019313:BRCA1 Protein; D000068579:Celecoxib / Q000494:pharmacology*; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D019313:BRCA1 Protein; C000605931:Brca1 protein, mouse; D052246:Cyclooxygenase 2 Inhibitors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D000068579:Celecoxib
keywords: COX-2 inhibitor; celecoxib; genetically engineered mouse model; obesity; ovarian cancer