title: Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib.
abstract: Higher cyclooxygenase-2 (COX-2) expression is clinically associated with more aggressive gliomas and is a strong predictor of poor survival. To determine whether oral administration of a COX-2-specific inhibitor can inhibit glial tumors, we analyzed the effect of celecoxib on the growth of 9L rat gliosarcoma cells that were orthotopically transplanted into rat brains. Oral administration of celecoxib beginning 1 day after implantation of 5 x 10(4) 9L rat gliosarcoma cells into rat brain reduced the incidence and size of tumors significantly. Immunohistochemical analysis of implanted gliosarcoma cells from rats treated with celecoxib showed lower levels of phospho-Akt, phospho-EGFR, Bcl-2, and Bcl-XL expression compared with untreated tumor cells. Gliosarcoma cells from treated rats had significantly more TUNEL- and caspase-3-positive cells and fewer PCNA-positive cells. These results demonstrate that selective COX-2 inhibitors may be useful as adjuvants and/or therapeutic agents to treat gliomas overexpressing COX-2.
authors.affiliation: Department of Neurosurgery, Samsung Medical Center and Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. nsnam@smc.samsung.co.kr
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Kwan
authors.initials: K
authors.lastname: Park
authors.forename: Chaehwa
authors.initials: C
authors.lastname: Park
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Sangjun
authors.initials: S
authors.lastname: Lee
authors.forename: Seung-Chyul
authors.initials: SC
authors.lastname: Hong
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Whan
authors.initials: W
authors.lastname: Eoh
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonnell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity; D005910:Glioma / Q000473:pathology*; D018316:Gliosarcoma; D020287:In Situ Nick-End Labeling; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib