[Roles of cyclooxygenase-2 and caspase-3 expression in pathogenesis of lung carcinoma: an experiment with rats].
OBJECTIVE
To investigate the dynamic expression of cyclooxygenase-2 (COX-2) and caspase-3 during the carcinogenesis, invasion and metastasis of 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN)-induced rat lung cancer and its significance.


METHODS
Iodized oil with MCA and DEN was instilled into the left bronchi of 80 Wistar rats to induce squamous cell lung carcinoma. Iodized oil without MCA and DEN was instilled into the left bronchi of 10 rats as control group. Sixteen rats in the experimental group and 2 rats in the control group were killed 10, 15, 35, 60, and 270 days after experiment respectively to undergo pathological examination. Immunohistochemistry was used to detect the protein expression of COX-2 and caspase-3 in the bronchial endothelial cells. Immunohistochemical scores (IHS) were calculated.


RESULTS
Pathological changes of different phases, such as hyperplasia of bronchial mucosal endothelial cells (14 cases), squamous metaplasia (25 cases), atypical proliferation (35 cases), carcinoma in situ (12 cases), infiltrative carcinoma (54 cases), and metastatic carcinoma (15 cases) appeared successively in the left lung mucosal endothelium of the experimental group. Weak expression of COX-2 protein was occasionally seen in the normal bronchial mucosal endothelium. COX-2 protein expression was becoming stronger and the IHS was becoming higher along with the development of carcinoma (P < 0.01). Caspase-2 protein expression was positive in 8 of the 10 (80%) of the control rats with an HIS of 5.92 +/- 0.9. And caspase-2 protein expression was becoming weaker along with the development of carcinoma (P < 0.01 or P < 0.05). Significant negative correlation was found between the COX-2 protein expression and caspase-3 expression (P < 0.01).


CONCLUSIONS
COX-2 and caspase-3 play important roles in the carcinogenesis of MCA and DEN-induced rat lung squamous cell carcinoma. COX-2 may take part in blocking cell apoptosis by inhibiting caspase-3 activity, thereby promoting the carcinogenesis of lung cancer. The imbalance between COX-2 and caspase-3 may be a critical factor affecting the biologic behavior of lung carcinogenesis, invasion and metastasis.
Chen
Fu-chun
FC
Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Zhejiang 317500, China.
Pan
Qi
Q
Zhang
Yu-xia
YX
Chen
Hong-lei
HL
Li
Hong-gang
HG
Tao
Hong-chao
HC
Yang
Fei
F
Xia
Dong
D
Liu
Ming-qiu
MQ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009362:Neoplasm Metastasis; D051381:Rats; D017208:Rats, Wistar
D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3