BACKGROUNDTo investigate the expression of cyclooxygenase-2 (COX-2) protein and inducible nitric oxide synthase (iNOS) protein during the experimental lung carcinogenesis in rats, as well as their association with microvessel density (MVD).

METHODSDiethylinitrosamine and 3-methylcholanthrene were instilled into the left lobar bronchus to induce lung squamous cell carcinoma in 88 Wistar rats, and 10 nomal rats as controls. COX-2, iNOS expression and MVD count of the specimens obtained from the rats were examined by immunohistochemistry.

RESULTSA total of 155 specimens of various pathological phase during the carcinogenesis were obtained: 14 hyperplasia, 25 squamous metaplasia, 33 dysplasia, 12 carcinoma in situ, 54 infiltration carcinoma, and 17 metastasis. The immunohistochemical score (IHS) of COX-2 significantly increased in dysplasia, carcinoma in situ and metastasis (P < 0.01,P < 0.05,P < 0.01). IHS of iNOS significantly increased in hyperplasia and metastasis (P < 0.05,P < 0.01 ). Remarkably increased MVD was found in carcinoma in situ, infiltration carcinoma and metastasis (P < 0.01, P < 0.01, P < 0.01). There was a positive correlation between COX-2 and iNOS (r=0.601 6,P < 0.001) expression. Expression of COX-2 or iNOS were remarkably related to MVD count (P < 0.01,P < 0.01)

CONCLUSIONSCOX-2 and iNOS may play important roles in the carcinogenesis of experimental rat lung squamous cell carcinoma as well as its progress, and it may be associated with stimulating angiogenesis.