Preventative effect of celecoxib in dimethylbenz[a]anthracene-induced ovarian cancer in rats
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The present study investigated the preventive effect of the cyclooxygenase (COX)-2 inhibitor, celecoxib, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer in a rat model.
A diet containing celecoxib (1500 ppm) was started 2 weeks before the introduction of DMBA. DMBA-soaked cotton threads were surgically applied to induce ovarian cancer in female Wistar rats. Tumor growth and survival were observed for 24 weeks.
During the study period, an overall tumor incidence of 97.5% was observed and 65% of tumors were ovarian adenocarcinoma. The celecoxib diet significantly reduced the incidence and size of DMBA-induced ovarian cancers and significantly improved survival of tumor-bearing rats. The preventive effect of celecoxib was associated with increased apoptosis.
DMBA-induced ovarian cancer in rats recapitulates many pathophysiological features of the human counterpart. Our results provide supportive evidence that celecoxib has a preventive effect on development of ovarian cancer in a rat model.
KeywordsOvarian cancer 7, 12-dimethylbenz[a]anthracene (DMBA) Cyclooxygenase 2 inhibitor Celecoxib Survival
XC and SZ designed the study. SZ, WQ, ZT, JW and KY participated in animal studies and related experiments. SZ, WS and XC analyzed data and wrote the manuscript. All authors read and approved the final manuscript.
This research is supported by Foundations of Medicine and Hygiene Science and Technology Planning Project of Zhejiang Province (2012KYB031) and Zhejiang Natural Science Foundation (LY14H160010).
Compliance with ethical standards
This study was approved by the Biomedical Research Ethics Committee of Shanghai Institute for Biological Science of Chinese Academy.
Consent for publication
Conflict of interest
The authors declare no competing interests.
- 2.American Cancer Society (2016) Cancer facts and figures 2016. American Cancer Society, AtlantaGoogle Scholar
- 4.Nishida T, Sugiyama T, Kataoka A, Ushijima K, Yakushiji M (1998) Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7,12-dimethylbenz[a]anthracene-coated suture: common epithelial tumors of the ovary in rats? Cancer 83(5):965–970CrossRefPubMedCentralGoogle Scholar
- 5.Crist KA, Zhang Z, You M, Gunning WT, Conran PB, Steele VE, Lubet RA (2005) Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture. Carcinogenesis 26(5):951–957. https://doi.org/10.1093/carcin/bgi039 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Suri A, Sheng X, Schuler KM, Zhong Y, Han X, Jones HM, Gehrig PA, Zhou C, Bae-Jump VL (2016) The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer. Oncotarget 7(26):39582–39594. https://doi.org/10.18632/oncotarget.8659 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Khan AA, Alanazi AM, Jabeen M, Hassan I, Bhat MA (2016) Targeted nano-delivery of novel omega-3 conjugate against hepatocellular carcinoma: regulating COX-2/bcl-2 expression in an animal model. Biomed Pharmacother 81:394–401. https://doi.org/10.1016/j.biopha.2016.04.033 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Hennequart M, Pilotte L, Cane S, Hoffmann D, Stroobant V, Plaen E, Eynde B (2017) Constitutive IDO1 expression in human tumors is driven by cyclooxygenase-2 and mediates intrinsic immune resistance. Cancer Immunol Res 5(8):695–709. https://doi.org/10.1158/2326-6066.CIR-16-0400 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Webb T, Carter J, Roberts JL, Poklepovic A, McGuire WP, Booth L, Dent P (2015) Celecoxib enhances [sorafenib + sildenafil] lethality in cancer cells and reverts platinum chemotherapy resistance. Cancer Biol Ther 16(11):1660–1670. https://doi.org/10.1080/15384047.2015.1099769 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Reyners AK, de Munck L, Erdkamp FL, Smit WM, Hoekman K, Lalisang RI, de Graaf H, Wymenga AN, Polee M, Hollema H, van Vugt MA, Schaapveld M, Willemse PH, DoCaCel Study G (2012) A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study. Ann Oncol 23(11):2896–2902. https://doi.org/10.1093/annonc/mds107 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Reddy BS, Hirose Y, Lubet R, Steele V, Kelloff G, Paulson S, Seibert K, Rao CV (2000) Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Can Res 60(2):293–297Google Scholar
- 29.Harris RE, Alshafie GA, Abou-Issa H, Seibert K (2000) Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Can Res 60(8):2101–2103Google Scholar
- 30.Grubbs CJ, Lubet RA, Koki AT, Leahy KM, Masferrer JL, Steele VE, Kelloff GJ, Hill DL, Seibert K (2000) Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Can Res 60(20):5599–5602Google Scholar
- 31.Cai F, Chen M, Zha D, Zhang P, Zhang X, Cao N, Wang J, He Y, Fan X, Zhang W, Fu Z, Lai Y, Hua ZC, Zhuang H (2017) Curcumol potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer. Oncotarget 8(70):115526–115545. https://doi.org/10.18632/oncotarget.23308 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Guo Q, Liu X, Lu L, Yuan H, Wang Y, Chen Z, Ji R, Zhou Y (2017) Comprehensive evaluation of clinical efficacy and safety of celecoxib combined with chemotherapy in management of gastric cancer. Medicine 96(51):e8857. https://doi.org/10.1097/MD.0000000000008857 CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8(3):289–293. https://doi.org/10.1038/nm0302-289 CrossRefPubMedPubMedCentralGoogle Scholar