The effect of selective cyclooxygenase-2 inhibitor nimesulide on breast cancer induced by dimethylbenzoic acid in rats / 中华外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>