title: Downregulation of NF-κB and PCNA in the regulatory pathways of apoptosis by cyclooxygenase-2 inhibitors in experimental lung cancer.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation, angiogenesis and by promoting apoptosis. The present study further explored the comparative role of a traditional NSAID, indomethacin and a newly developed coxib, etoricoxib against 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung carcinogenesis in rats. Morphological and histological analysis revealed the occurrence of tumors and lesions along with constricted alveolar spaces in the DMBA treated animals which were largely corrected both by indomethacin and etoricoxib. COX-1 was found to be uniformly expressed in all the groups while COX-2 levels were raised prominently in the DMBA treated animals. Proliferation, as studied by PCNA expression was found to be markedly increased in the DMBA group as compared to the others. Increased NF-κB expression in the DMBA group was found to correct with the co-administration of NSAIDs. Also, fluorescent co-staining of the isolated lung cells revealed a significantly decreased apoptosis and altered mitochondrial membrane potential. In conclusion, these parameters indicate to the chemopreventive action of the two NSAIDs studied in lung cancer and as their mechanism of action suggests, can be achievable both by COX-dependent and COX-independent pathways.
authors: Department of Biophysics, Panjab University, Chandigarh, India.
authors: Shruti
authors: S
authors: Setia
authors: Sankar Nath
authors: SN
authors: Sanyal
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D000077613:Etoricoxib; D015972:Gene Expression Regulation, Neoplastic; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D013450:Sulfones / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D011725:Pyridines; D013450:Sulfones; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2; D000077613:Etoricoxib