A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas

Abstract

Although dexamethasone is very effective for controlling peritumoral cerebral edema, it is associated with distressing side effects that decrease the quality of life for many patients. One potential mechanism to explain the ability of dexamethasone to repair blood-brain barrier dysfunction is through the inhibition of cyclooxygenase-2 (COX-2). The purpose of this study was to determine in a rat brain tumor model whether SC-236, a selective COX-2 inhibitor, is as effective as dexamethasone. Twenty-nine adult male Fischer 344 rats were implanted with intracerebral 9L gliosarcomas and divided into 3 treatment groups. One group (n = 9) served as controls, another (n = 9) was treated with dexamethasone (3 mg/kg p.o. daily), and a third group (n = 11) received SC-236 (3 mg/kg p.o. daily). A survival study was performed. The median survival in the control group was 16 days, compared with 23 days for the dexamethasone group and 23 days for the COX-2 inhibitor group. Kaplan-Meier analysis on pairwise group comparisons showed improved survival that was statistically significant for each treatment group compared with the control group (log-rank test P = 0.009 for dexamethasone to control and P = 0.005 for COX-2 to control), and no significant difference in survival for the COX-2 compared with dexamethasone (log-rank test P = 0.2). These results suggest that a selective COX-2 inhibitor appears to be as effective as dexamethasone in prolonging survival in a rat brain tumor model.

Influence of Caloric Restriction on Constitutive Expression of NF-κB in an Experimental Mouse Astrocytoma

“…Activated NF-κB translocates to the nucleus, binds to DNA, and then activates a number of pro-inflammatory molecules like COX-2, TNF-α, IL-6, IL-8, MMP-9 [26], [37]. COX-2 expression plays a key role in the development of edema in brain tumors [9], [38].…”

Multimodality Imaging of Abnormal Vascular Perfusion and Morphology in Preclinical 9L Gliosarcoma Model

“…Although there are several possible explanations for the reduced potency of dexamethasone to inhibit VEGF expression in vivo , the most likely is that a considerable proportion of tumor cells suffer from hypoxia especially at later stages of tumor growth. Another potential mechanism is the ability of dexamethasone to repair blood-brain barrier dysfunction through the inhibition of cyclooxygenase-2, which also results in prolonged survival [20]. In addition, tumor size and vascular density were reduced in dexamethasone treated rats implanted with 9L gliosarcoma cells [16], [21], [22] and C6 glioma cells [22] after intraperitoneal administration of 3 mg/kg/day.…”

Current advances in understanding and managing secondary brain metastasis

“…AZD2171, a multitargeted tyrosine kinase inhibitor, can alleviate edema, a major cause of morbidity in glioblastoma, and is associated with a steroid-sparing effect in these patients [49]. In one study, the selective COX-2 inhibitor SC-236 appeared to be as effective as dexamethasone in prolonging survival in a rat brain tumor model [50]. Another selective COX-2 inhibitor, celecoxib, was found to suppress the growth and metastasis of human pancreatic cancer by inhibition of VEGF expression and tumor microvessel formation.…”