gms | German Medical Science

Objective: Human meningiomas are mostly benign, but they may relapse or are not fully resectable because of anatomical restrains. Alternative, systemic chemotherapeutical treatment has been largely disappointing. Epidemiologic studies have suggested that inflammatory processes may be involved in tumor progression and several studies recently supported the use of non steroidal anti-inflammatory drugs, such as the selective cyclooxygenase-2 (COX-2) inhibitor, for treatment of different cancer types. The treatment of benign meningiomas with the COX-2 inhibitor celecoxib showed an inhibitory effect of tumor growth in vitro and in vivo after subcutaneous heterotopic transplantation into mouse. We here tested the effects of celecoxib on human meningioma after orthotopic transplantation into the prefrontal cortex of nude mice after confirming the inhibitory in vitro effect on these cells.

Methods: We used primary cell cultures of four benign meningiomas, which were stereotactically implanted into the prefrontal cortex of 2–5 NMRI nu/nu mice. The animals were then orally treated with 0 ppm, 750 ppm or 1500 ppm celecoxib over a period of three months. Thereafter, the mice were sacrificed and blood was taken to analyze the concentrations of celecoxib. For histological analysis formalin-fixed and paraffin-embedded brains were stained with hematoxylin and eosin to measure the tumor volume and immunohistochemically processed to analyze COX-2, proliferation index (PI), intratumoral microvessel density (iMVD) and vascular endothelial growth factor (VEGF)-expression.

Results: Treatment with celecoxib had no effect on intracranial tumor volume, although in vitro we found a dose dependent inhibitory effect on cell cultures from these meningiomas and also found sufficient concentration in both blood plasma and in the brain tissue after treatment with celecoxib. Additionally, celecoxib had no effect on COX-2- and VEGF-expression, and on the PI and iMVD in meningiomas of mice.

Conclusions: Our findings suggest that celecoxib may not be effective on meningioma growth in clinical settings. In general, these results may indicate that the effect of treatment on brain tumors should not only be tested in a heterotopic environment, but rather in the orthotopic intracranial location of these tumors.

This study was supported by a grant from Else Kröner-Fresenius-Stiftung, Bad Homburg vor der Höhe, Germany