Celecoxib inhibits meningioma tumor growth in a mouse xenograft model

Abstract

BACKGROUND.Treatments for recurrent meningiomas are limited. We previously demonstrated universal expression of COX‐2 in meningiomas and dose‐dependent growth inhibition in vitro with celecoxib, a COX‐2 inhibitor. We therefore tested the effects of celecoxib on meningioma growth in a mouse xenograft model.METHODS.Meningioma cell lines (IOMM‐Lee, CH157‐MN, WHO grade I primary cultured tumor) were transplanted into flanks of nude mice fed mouse chow with celecoxib at varying concentrations (0, 500, 1000, 1500 ppm) ad libitum. Tumors were measured biweekly and processed for MIB‐1, Factor VIII, COX‐2, and VEGF, and assayed with transferase‐mediated dUTP‐biotin nick‐end labeling (TUNEL).RESULTS.Celecoxib reduced growth of mean tumor volume by 66% (P < .05), 25% (P > .05), and 65% (P < .05) compared with untreated controls in IOMM‐Lee, CH157‐MN, and benign tumors, respectively. IOMM‐Lee tumors removed from celecoxib treatment regained a growth rate similar to the control. Blood vessel density decreased and apoptotic cells increased in treated flank tumors. Diminished COX‐2 expression and VEGF were observed in treated IOMM‐Lee tumors. Mean plasma celecoxib levels were 845, 1540, and 2869 ng/mL, for low‐, medium‐, and high‐dose celecoxib, respectively.CONCLUSIONS.Celecoxib inhibits meningioma growth in vivo at plasma levels achievable in humans. Celecoxib‐treated tumors were less vascular with increased apoptosis. IOMM‐Lee tumors treated with celecoxib showed decreased COX‐2 and VEGF expression. COX‐2 inhibitors may have a role in the treatment of recurrent meningiomas. Cancer 2007;109:588–597. © 2006 American Cancer Society.

Effects of cyclooxygenase inhibitors on survival time in ovarian cancer xenograft-bearing mice

“…In the same study, using western blotting analysis, we identified that COX-1 and COX-2 protein levels were reduced in the combination group cells in comparison with those in the control group (20). The reason for the inhibition of COX-1 and/or COX-2 mRNA and protein expression in neoplastic tissues may be due to the inhibition of angiogenesis, induction of apoptosis and/or antiproliferative effects (6,8,10). The antitumor effects of coxibs have long been suggested to depend on the inhibition of COX activity and PG synthesis.…”

“…PGE 2 is produced from arachidonic acid by one of two enzymes: COX-1 or COX-2. There is increasing evidence that PGE 2 contributes to tumor progression by promoting tumor angiogenesis and inducing tumor cell apoptosis (8,26,27). Our same study that focused on the potential mechanisms revealed that coxibs suppress ovarian tumor growth by influencing cell proliferation and apoptosis (20).…”

“…Clinical and preclinical studies have indicated that COX-2 inhibitors are rapidly emerging as an excellent target for prevention and/or treatment of human cancers (7-10) due to their antiproliferative and antiangiogenic effects and their role in enhanced immune surveillance (8,9). Few studies have also concluded that COX-1 inhibitors are able to reduce tumor growth by decreasing cell proliferation and accelerating apoptosis (6,10).…”

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

“…Factor VIII-related antigen, also known as von Willebrand factor (vWf), is synthesized in ECs and megakaryocytes and it mediates platelet adhesion to the walls of injured vessels. Immunohistochemical detection of CD31 and F VIII RAg has been used extensively to quantify angiogenesis of xenograft tumors in immunodeficient animal models carrying various human tumor cell loads (Vanzulli et al 1997, Fulzele et al 2006, Muruganandham et al 2006, Ragel et al 2007). …”

Celecoxib/PLGA Suprime Angiogénesis y Metástasis Pulmonar de un Cáncer Mamario Murino Experimental

“…Las células TA3-MTX-R fueron seleccionadas a partir de un tumor ascítico TA3 in vivo, de acuerdo a lo descrito por Rosas et al (2013), en una concentración final de 2x10 6 células por mL de la suspensión tumoral. , el cual fue diluido en el agua destilada hasta alcanzar la concentración media de 1000 ppm, según lo descrito por Ragel et al (2007 Las muestras de los pulmones fueron fijados en formalina tamponada al 10 % por 48 h, realizándose el procesamiento histológico necesario para obtener cortes de 5 µm, los que fueron teñidos con H&E y Tricrómico de Arteta, según lo descrito por Rosas et al (2013). Se agregaron muestras de pulmón sano de ratón, como control.…”