Effects of Celecoxib in Human Retinoblastoma Cell Lines and in a Transgenic Murine Model of Retinoblastoma

Abstract

Abstract: : Purpose:Celecoxib is a COX–2 inhibitor and antiangiogenic agent that has demonstrated significant anticancer effects in cell culture and animal studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, we investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease. Methods: Antiproliferative effects of celecoxib were evaluated in Y79 and Weri–RB1 human retinoblastoma cell lines by WST–1 Cell Proliferation assay. For animal study, two groups of 24 eight–week–old LHß–TAg transgenic mice were treated with celecoxib or with vehicle control. Mice in the celecoxib group received 250 mg/kg celecoxib by oral gavage once daily, 5 days/week (Monday–Friday) for 6 weeks. Control mice received vehicle alone on the same treatment schedule. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumor burden was quantified by histopathological analysis. Results: Celecoxib did not inhibit proliferation of Y79 or Weri–RB1 cells, even at concentrations that far exceeded clinically achievable levels. We also found no statistically significant difference in ocular tumor burden between celecoxib–treated and control mice. Mean ocular tumor burden per mouse was 114,560 ± 156,340 square pixels and 99,793 ± 128,596 square pixels in the treatment and control groups, respectively (p<0.73). Conclusions: Celecoxib was ineffective at inhibiting proliferation of human retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumor growth in a murine model of this disease. On the basis of these findings, celecoxib is less likely to have clinical utility in the management of retinoblastoma.

Keywords: tumors • retinoblastoma • drug toxicity/drug effects