[The effect of selective cyclooxygenase-2 inhibitor nimesulide on breast cancer induced by dimethylbenzoic acid in rats].
OBJECTIVE
To study the effect of nimesulide (NIM) on the tumorigenesis of mammary tumors induced by dimethylbenzoic acid (DMBA), and to investigate possible mechanisms of NIM against tumors.


METHODS
The studied rats were randomly divided into four groups: experimental control group, NIM group, diet and drug of NIM control group. The incidence of mammary tumor was observed. RT-PCR, Western blot were used to detect 8 cancerous tissues in every group, randomly. The expressions of cylooxygenase-2 (COX-2) were assessed by immunohistochemistry. The levels of prostaglandin E(2) (PGE(2)) in blood plasma and tumor tissues were determined by means of radio-immunity assay. The apoptosis index and the proliferation index were evaluated by TUNEL assay, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), respectively.


RESULTS
The incidence of mammary tumor was 69.2% in experimental control group, 40.3% in NIM group. There was obviously decreased incidence in NIM group; The expressions of COX-2 mRNA and protein were significantly down-regulated in NIM group compared with experimental control group. The increased levels of PGE(2) synthesis in blood plasma and tumor tissues were significantly decreased by administering NIM (P < 0.05). The apoptosis index was obviously higher, the proliferation index was markedly less in NIM group than experimental control group.


CONCLUSIONS
Nimesulide could inhibit the tumorigenesis and development of DMBA-induced mammary tumors by inhibition of proliferation and induction of apoptosis. COX-2 and COX-2-mediated PGE(2) synthesis may play an important role in rat DMBA-induced breast cancer.
Guo
Gui-long
GL
Department of Oncological Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. guoguilong@sina.com.cn
Zhang
Xiao-hua
XH
Yao
Zhen-xiang
ZX
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D015127:9,10-Dimethyl-1,2-benzanthracene; D015232:Dinoprostone; C012655:nimesulide