Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma.
OBJECTIVE
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 LHbeta-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.


CONCLUSIONS
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.
Tong
C T
CT
Ocular Oncology Unit, UCSF Department of Ophthalmology, 10 Koret Way, Box 0730, San Francisco, CA 94143, USA.
Howard
S A
SA
Shah
H R
HR
Van Quill
K R
KR
Lin
E T
ET
Grossniklaus
H E
HE
O'Brien
J M
JM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000627:therapeutic use*; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*; D017211:Treatment Failure
D020533:Angiogenesis Inhibitors; D000952:Antigens, Polyomavirus Transforming; D037101:Luteinizing Hormone, beta Subunit; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib