Induction of pulmonary carcinogenesis in Wistar rats by a single dose of 9, 10 dimethylbenz(a)anthracene (DMBA) and the chemopreventive role of diclofenac.
OBJECTIVE
To evaluate the chemopreventive efficacy of Diclofenac, a preferential cyclooxygenase-2 (COX-2) inhibiting non steroidal anti-inflammatory drug (NSAID) in the 9, 10 Dimethylbenz(a)anthracene (DMBA) induced experimental lung carcinogenesis.


METHODS
Animals were divided into 4 groups. Control group received normal saline intratratracheally. DMBA group was given DMBA (20 mg/kg of body weight) in the similar manner. DMBA+Diclofenac group was given daily oral dose of Diclofenac (8 mg/kg of body weight) in addition to DMBA while the last group received Diclofenac only. Animals were sacrificed after 24 weeks. COX-2 expression was studied by immunohistochemistry (IHC) and Western immunoblotting. For apoptosis study DNA fragmentation on agarose gel and florescent staining of alveolar macrophages were done.


RESULTS
The incidence and burden of tumor were reduced by the Diclofenac treatment. Diclofenac caused the reduction in the COX-2 levels which were increased in the DMBA treated group. It also caused the induction of apoptosis as seen by both techniques.


CONCLUSIONS
From all these results it can be concluded that Diclofenac might have a chemopreventive role for lung carcinogenesis which is mediated by suppression of COX-2 enzyme and induction of apoptosis.
Thakur
Poonam
P
Department of Biophysics, Panjab University, Chandigarh, India. poonamthkur@gmail.com
Sanyal
S N
SN
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat