Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib.
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.
Nam
Do-Hyun
DH
Department of Neurosurgery, Samsung Medical Center and Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. nsnam@smc.samsung.co.kr
Park
Kwan
K
Park
Chaehwa
C
Im
Young-Hyuck
YH
Kim
Mi-Hyun
MH
Lee
Sangjun
S
Hong
Seung-Chyul
SC
Shin
Hyung-Jin
HJ
Kim
Jong-Hyun
JH
Eoh
Whan
W
McDonnell
Timothy J
TJ
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*
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib