Chemopreventive action of non-steroidal anti-inflammatory drugs in 9,10-dimethylbenzanthracene induced lung carcinogenesis in BALB/C mice: Expression of COX-1, COX-2 and Nf-κB

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) play an effective chemopreventive action against a variety of cancers. The present study aimed at targeting pro-inflammatory cyclooxygenase (COX) and NF-kB mediated inflammatory pathways in 9,10-dimethylbenzanthracene (DMBA) induced lung cancer in BALB/C mice and chemoprotective action of NSAIDs. Animals were divided into five groups and treated with NSAIDs, intratracheally, daily for a period of 18 weeks. Group 1 as control, received vehicle treatment; Group 2 received single dose of DMBA (10mg/kg bw); Group 3, 4 and 5 besides DMBA treatment, also received Aspirin (60mg/kg bw), Celecoxib (6.0mg/kg bw) and Etoricoxib (0.6mg/kg bw), respectively. DMBA induce DNA damage, apoptosis and expression of COX-1, COX-2 and NF-κB using immunofluorescence and blot analysis were done. The present study demonstrated the formation of micronuclei, over-expression of COX-2 and NF-κB in DMBA induced lung tumorigenesis and thereby suggesting a marked role of inflammation in the tumour progression. Results indicate the formation of micronuclei in DMBA group, which were significantly reduced in aspirin treated group, and totally absent in the celecoxib and etoricoxib groups. In conclusion, co-administration of etoricoxib and celecoxib has significantly reduced the inflammatory potential of the growing neoplasm in DMBA induced lung cancer in male BALB/C mice.