The cyclooxygenase-2 inhibitor etoricoxib is a potent chemopreventive agent of colon carcinogenesis in the rat model.
Cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers, including colon cancer, and therefore the potential ability of a selective COX-2 inhibitor, etoricoxib, is considered in the prevention of the 1,2-dimethyl hydrazine (DMH)-induced colon carcinogenesis in the rat model. DMH was injected s.c. for 6 weeks, whereas etoricoxib was fed orally to the rats on a daily basis. The results showed that DMH produced a very high number of multiple plaque lesions (MPLs), putative neoplastic biomarkers, localized throughout the colon, whereas considerable regression was observed with etoricoxib treatment. In addition, the etoricoxib group was the only group that exhibited very few of these lesions. Histopathological analysis revealed extreme dysplasia, a few adenomas, and other carcinogenic changes in the DMH group, which are distinctly absent in the etoricoxib-treated group. COX-2 was also seen to be highly expressed following DMH treatment. The DMH treatment caused very few apoptotic cells, as determined by the TUNEL assay of the colonic mucosa in paraffin sections whose number greatly increased following etoricoxib treatment. Because all these changes were clearly reversed by etoricoxib in DMH-treated animals, and the use of etoricoxib alone did not produce a neoplastic effect per se, it appears that etoricoxib, a selective COX-2 inhibitor, might be a safe and potentially chemopreventive agent in colon cancer.
Saini
Manpreet Kaur
MK
Department of Biophysics, Panjab University, Chandigarh-160014, India.
Sharma
Pinky
P
Kaur
Jasmeet
J
Sanyal
Sankar Nath
SN
D019813:1,2-Dimethylhydrazine; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077613:Etoricoxib; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D019813:1,2-Dimethylhydrazine; D000077613:Etoricoxib