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Published on: September 30, 2016
Celecoxib induces regression of putative preneoplastic lesions in rat liver
Jaime Arellanes-Robledo1, Lucrecia Márquez-Rosado, Julio Isael Pérez-Carreón
1Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), Av. IPN No. 2508. Col. San Pedro Zacatenco, C.P. 07360, México, DF.
Background:
Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, may reduce the risk and mortality of certain types of human cancer. The chemopreventive effect of celecoxib on preneoplastic lesions induced by chemical hepatocarcinogenesis was investigated.
Materials And Methods:
Male Sprague Dawley rats were fed a celecoxib-supplemented diet between days 18 and 26 post-initiation (1500 ppm) and sacrificed on day 26. The effects of celecoxib on proliferation, apoptosis, COX-2 activity and liver function were evaluated by immunohistochemistry, TUNEL assay, enzyme-immunoassay and spectrophotometry, respectively.
Results:
Celecoxib decreased, in area and number, gamma-glutamyltranspeptidase and glutathione S-transferase placental-positive lesions, below levels found after 18 days, by 55.2% and 62.2%, and by 50.5% and 71.1%, respectively, (p < 0.05). Celecoxib neither induced apoptosis nor altered the levels of prostaglandin E2, bilirubin or alanine aminotransferase in the plasma; however, proliferating cell nuclear antigen and cyclin D1 decreased by 77.7% and 94.9%, respectively, (p < 0.05).
Conclusion:
Celecoxib regresses existing preneoplastic liver lesions through antiproliferative processes, without altering liver function.
Insights
Celecoxib, a COX-2 inhibitor, effectively regresses preneoplastic liver lesions by reducing cell proliferation. This study shows celecoxib
Area of Science:
- Hepatocarcinogenesis research
- Cancer chemoprevention strategies
- Pharmacological effects on liver lesions
Background:
- Cyclooxygenase-2 (COX-2) inhibitors, like celecoxib, show potential in reducing cancer risk and mortality.
- Investigating the chemopreventive efficacy of celecoxib on chemically induced preneoplastic liver lesions.
Purpose of the Study:
- To evaluate the effect of celecoxib on the regression of preneoplastic liver lesions.
- To assess celecoxib's impact on cellular proliferation, apoptosis, COX-2 activity, and liver function.
Main Methods:
- Male Sprague Dawley rats were administered a celecoxib-supplemented diet.
- Lesion analysis included quantification of gamma-glutamyltranspeptidase and glutathione S-transferase placental-positive foci.
- Cellular proliferation and apoptosis were assessed using immunohistochemistry and TUNEL assays, respectively.
Main Results:
- Celecoxib significantly decreased the area and number of preneoplastic liver lesions (p < 0.05).
- A marked reduction in proliferating cell nuclear antigen and cyclin D1 indicated an antiproliferative effect.
- No significant alterations in apoptosis, prostaglandin E2, bilirubin, or alanine aminotransferase levels were observed.
Conclusions:
- Celecoxib promotes regression of existing preneoplastic liver lesions.
- The regression occurs via antiproliferative mechanisms.
- Celecoxib does not adversely affect overall liver function.
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