Chemopreventive effect of celecoxib and expression of cyclooxygenase‐1 and cyclooxygenase‐2 on chemically‐induced rat mammary tumours

International Journal of Experimental Pathology - Tập 83 Số 4 - Trang 173-182 - 2002
Tae Jung Jang1, Ho Guen Jung, Ki Hoon Jung, Min Ku O
1Department of Pathology, Dongguk University College of Medicine, Kyongju, Kyongbuk, Korea. [email protected]

Tóm tắt

Summary.We investigated the chemopreventive effect of celecoxib on 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced rat mammary tumours and also the expression and immunolocalization of cyclooxygenase‐1 (COX‐1) and COX‐2 in the various stages of rat mammary carcinogenesis. Rats were divided into normal control group, DMBA‐control group, 500 p.p.m. celecoxib‐treated group, and 1500 p.p.m. celecoxib‐treated group. Both incidence and multiplicity values of tumour for rats treated with celecoxib were less than those in rats of the DMBA‐control group. The level of prostaglandin E2 was higher in tumours of the DMBA‐control and both celecoxib‐treated groups compared to normal mammary glands of each group. In Western blot analysis, all tumours of the DMBA‐control group expressed COX‐1, whereas normal mammary glands showed insignificant expression. COX‐2 expression was observed in 67% of the DMBA‐control group and 20% of both celecoxib‐treated groups and was absent in normal mammary glands. COX‐1 protein was localized in the nuclear membrane and cytoplasm of epithelial tumour cells abutting on glandular lumen, stromal cells, and endothelial cells. COX‐2 protein was detected in the perinuclear cytoplasm of tumour cells bordering on glandular lumen and surrounding stroma, stromal cells, and vascular smooth muscle. In the DMBA‐control group, invasive carcinoma cells showed higher positive immunoreactivity of COX‐2 than carcinomas in situ and atypical tumours. Tumours displayed an increased number of mast‐like cells with COX‐2 expression in comparison to carcinomas in situ. Our results suggest that COX‐1 and COX‐2 expression in tumour cells and stromal cells play an important role in the various stages of DMBA‐induced rat mammary carcinogenesis. In addition, we reconfirm that celecoxib reduces the growth of DMBA‐induced rat mammary tumours.

Từ khóa


Tài liệu tham khảo

Aaltomaa S., 1993, Mast cells in breast cancer, Anticancer Res., 13, 785

10.1101/gad.13.11.1382

10.1111/j.1600-0560.1998.tb01683.x

10.1093/jnci/88.14.988

10.1165/ajrcmb.18.4.2939

Fendl K.C., 1992, Role of tamoxifen in the induction of hormone‐independent rat mammary tumours, Cancer Res., 52, 235

10.1093/carcin/19.11.1939

Garay C.A., 1999, Chemoprevention of colorectal cancer: dietary and pharmacologic approaches, Oncology, 13, 89

Hamid R., 1999, Inhibition by dietary menhaden oil of cyclooxygenase‐1 and 2 in N‐nitrosomethylurea‐induced rat mammary tumours, Int. J. Oncol., 14, 523

Harris R.E., 2000, Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor, Cancer Res., 60, 2101

10.1097/00001648-199603000-00017

10.1016/0005-2760(95)00194-8

10.1038/sj.bjc.6690224

10.1093/jnci/90.6.455

Jacoby R.F., 2000, The cyclooxygenase‐2 inhibitor celecoxib is a potent preventive and therapeutic agent in the Min mouse model of adenomatous polyposis, Cancer Res., 60, 5040

Kawamori T., 1998, Chemoprevention activity of celecoxib, a specific cyclooxygenase‐2 inhibitor, against colon carcinogenesis, Cancer Res., 58, 409

10.1073/pnas.93.10.4816

10.1074/jbc.M010787200

10.1111/j.1349-7006.2000.tb01030.x

10.1016/S0952-3278(96)90122-2

Norrby K., 1993, Role of mast cells in mitogenesis and angiogenesis in normal tissue and tumour tissue, Adv. Biosci., 89, 71

10.1002/1097-0142(20010515)91:10<1876::AID-CNCR1209>3.0.CO;2-H

10.1136/bmj.299.6710.1247

Parrett M.L., 1999, Comparative ability of ibuprofen and N‐(4‐hydroxyphenyl) retinamide to inhibit development of rat mammary adenocarcinomas associated with differential inhibition of gene expression of cyclooxygenase isoforms, Anticancer Res., 19, 5079

Parrett M.L., 1997, Cyclooxygenase‐2 gene expression in human breast cancer, Int. J. Oncol., 10, 503

Rao C.V., 1995, Chemoprevention of colon carcinogenesis by sulindac, nonsteroidal anti‐inflammatory agent, Cancer Res., 55, 1464

10.1093/carcin/14.8.1493

10.1006/bbrc.1999.1658

10.1016/S0304-3835(97)00387-X

10.1006/pmed.1995.1018

Russo J., 1990, Comparative study of human and rat mammary tumourigenesis, Laboratory Invest., 62, 244

10.1006/gyno.1999.5690

Sawaoka H., 1999, Cyclooxygenase inhibitors suppress angiogenesis and reduce tumour growth in vivo, Laboratory Invest., 79, 1469

10.1097/00001648-199403000-00003

10.1073/pnas.91.25.12013

10.1093/carcin/16.9.2193

10.1093/carcin/20.2.185

10.1002/(SICI)1098-2744(199903)24:3<177::AID-MC4>3.0.CO;2-6

10.1038/nm0901-1048

10.1002/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B

10.1136/thx.52.11.940

Thun M.J., 1993, Aspirin use and risk of fatal cancer, Cancer Res., 53, 1322

10.1056/NEJM199112053252301

10.1007/978-1-4899-1813-0_25

10.1016/S0092-8674(00)81433-6

10.1038/newbio231232a0

10.1038/367215a0

Westphal E., 1891, Farbenanalytische Untersuchungen. zur Histologie und Klinik des Blutes: Gesammelte Mitt(h)eilungen, 17

Thông tin
Thông tin xuất bản

International Journal of Experimental Pathology

Tập 83 Số 4

173-182

Thông tin tác giả