title: Chemopreventive action of diclofenac in dimethybenzanthracene induced lung cancer in female Wistar rat.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective antineoplastic agents that block prostaglandin formation by inhibiting the enzyme cyclooxygenase (COX), which exists in two isoforms, COX-1 and COX-2. COX-2 is over expressed in lung cancer. The present study evaluates the chemopreventive efficiency of diclofenac, which is a preferentially selective COX-2 inhibitor in lung cancer. Female Wistar rats were divided into 4 groups. Group 1 served as control and received saline intratracheally, once. In group 2 lung cancer was induced by a single intratracheal instillation of dimethybenz(a)anthracene (DMBA) (20 mg/kg body weight). Group 3 was given the intervention of diclofenac (8 mg/kg body weight) daily by oral gavage, in addition to DMBA. Group 4 received diclofenac alone. After 18 weeks of treatment, animals were sacrificed and various studies done. COX-2 expression as seen by western immunoblot and immunohistochemistry (IHC) was increased in the DMBA group, while diclofenac intervention was able to bring down the levels of the enzyme. Apoptosis studies by DNA fragmentation, TUNEL and fluorescent dyes reveal the lowered number of apoptotic cells in group 2. The levels were restored by diclofenac treatment in group 3. There was also a significant reduction in tumor incidence in DMBA+Diclofenac treated animals. All these results indicate that diclofenac acts as an effective chemopreventive agent that mediates its effects by the induction of apoptosis in cancer tissue and suppression of COX-2 enzyme.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Thakur
authors.forename: Sankar Nath
authors.initials: SN
authors.lastname: Sanyal
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000032:analysis; D004008:Diclofenac / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; D004008:Diclofenac; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2