Expression of inflammation related enzymes during experimental rat lung carcinogenesis.
OBJECTIVE
To investigate the expression of two inflammation related enzymes - cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) during the experimental rat lung carcinogenesis.


METHODS
Eighty Wistar rats were instilled with 3-methylcholanthrene (MCA) and diethylinitrosamine (DEN) into the left lobar branchus to induce lung squamous cell carcinoma. To obtain specimen in every pathological phase during the carcinogenesis, these rats were sacrificed at different intervals. The expression of COX-2 and iNOS in every pathological phase during the carcinogenesis were examined by immunohistochemical method. The immunohistochemical scores (IHS) were calculated by combining an estimate of the percentage of immunoreactive cells with that of the stain intensity.


RESULTS
155 specimens of every pathological phase during the carcinogenesis showed: hyperplasia 14, squamous metaplasia 25, dysplasia 33, carcinoma in situ 12, infiltrating carcinoma 54 and metastasis 17. Inflammation and elevated expressions of COX-2 and iNOS were shown in the precancerous lesions. The COX-2 IHS was significantly increased in dysplasia, carcinoma in situ and metastasis (P < 0.01, P < 0.05, P < 0.01 respectively). The iNOS IHS significantly increased in hyperplasia and metastasis (P < 0.05, P < 0.01 respectively). There was a positive correlation between the expression of COX-2 and iNOS (gamma = 0.601 6, P < 0.001).


CONCLUSIONS
COX-2 and iNOS, two inflammation related enzymes, playing important roles in the carcinogenesis of MCA and DEN, induce rat lung squamous cell carcinoma as well as its metastasis. The relation between inflammation and carcinogenesis may partly be explained by the elevated expression of these two enzymes. Nonsteroidal antiinflammatory drug (COX-2 inhibitors) and iNOS inhibitors may possess antitumor activities because of their prevention of bronchial dysplasia, carcinogenesis and metastasis.
Li
Honggang
H
Department of Pathology, Medical College, Wuhan University, Wuhan 430071, China.
Chen
Fuchun
F
Yu
Lunyin
L
Liu
Mingqiu
M
Chen
Honglei
H
Zhang
Yuxia
Y
Liu
Xuan
X
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000009:adverse effects; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D007527:Isoenzymes; D008748:Methylcholanthrene; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases