Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma
- 1Ocular Oncology Unit, Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA
- 2Department of Biopharmaceutical Sciences, University of California at San Francisco, San Francisco, CA, USA
- 3Department of Ophthalmology, Emory University, Atlanta, GA, USA
- 4Ocular Oncology Unit, UCSF Department of Ophthalmology, 10 Koret Way, Box 0730, San Francisco, CA, USA
- Correspondence to: Joan M O’Brien MD, Ocular Oncology Unit, UCSF Department of Ophthalmology, 10 Koret Way, Box 0730, San Francisco, CA 94143, USA; alejaitsa.ucsf.edu
- Accepted 1 March 2005
Abstract
Background/aim: Celecoxib, a cyclooxygenase-2 inhibitor and antiangiogenic agent, has demonstrated potent anticancer effects in preclinical studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, the authors investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease.
Methods: Growth inhibitory 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, 8 week old LHβ-TAg transgenic mice were treated with celecoxib (250 mg/kg, orally once a day) or vehicle control, 5 days/week for 6 weeks. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumour burden was quantified by histopathological analysis.
Results: Celecoxib did not inhibit proliferation of Y79 or Weri-RB1 cells, even at concentrations far exceeding clinically achievable levels. No significant difference in ocular tumour burden between celecoxib treated and control mice (p = 0.73) was found.
Conclusion: Celecoxib was ineffective at inhibiting proliferation of retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumour growth in a murine model of this disease. On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma.
- COX-2, cyclooxygenase-2
- EBRT, external beam radiotherapy
- LHβ, luteinising hormone β subunit
- NSAID, non-steroidal anti-inflammatory drug
- PCR, polymerase chain reaction
- PGs, prostaglandins
- VEGF, vascular endothelial growth factor
- celecoxib
- cell lines
- drug evaluation
- mice
- retinoblastoma
- COX-2, cyclooxygenase-2
- EBRT, external beam radiotherapy
- LHβ, luteinising hormone β subunit
- NSAID, non-steroidal anti-inflammatory drug
- PCR, polymerase chain reaction
- PGs, prostaglandins
- VEGF, vascular endothelial growth factor
- celecoxib
- cell lines
- drug evaluation
- mice
- retinoblastoma
Footnotes
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Competing interests: none declared







