Celecoxib inhibits meningioma tumor growth in a mouse xenograft model

Brian T. Ragel, Randy L. Jensen, David L. Gillespie, Stephen M. Prescott, William T. Couldwell

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48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)588-597
Number of pages10
JournalCancer
Volume109
Issue number3
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

Fingerprint

Celecoxib
Meningioma
Heterografts
Growth
Neoplasms
Vascular Endothelial Growth Factor A
Cyclooxygenase 2 Inhibitors
Blood Vessels

Keywords

  • Celecoxib
  • COX-2
  • Cyclooxygenase-2
  • In vivo
  • Meningioma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ragel, B. T., Jensen, R. L., Gillespie, D. L., Prescott, S. M., & Couldwell, W. T. (2007). Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. Cancer, 109(3), 588-597. https://doi.org/10.1002/cncr.22441

Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. / Ragel, Brian T.; Jensen, Randy L.; Gillespie, David L.; Prescott, Stephen M.; Couldwell, William T.

In: Cancer, Vol. 109, No. 3, 01.02.2007, p. 588-597.

Research output: Contribution to journalArticle

Ragel, BT, Jensen, RL, Gillespie, DL, Prescott, SM & Couldwell, WT 2007, 'Celecoxib inhibits meningioma tumor growth in a mouse xenograft model', Cancer, vol. 109, no. 3, pp. 588-597. https://doi.org/10.1002/cncr.22441
Ragel BT, Jensen RL, Gillespie DL, Prescott SM, Couldwell WT. Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. Cancer. 2007 Feb 1;109(3):588-597. https://doi.org/10.1002/cncr.22441
Ragel, Brian T. ; Jensen, Randy L. ; Gillespie, David L. ; Prescott, Stephen M. ; Couldwell, William T. / Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. In: Cancer. 2007 ; Vol. 109, No. 3. pp. 588-597.
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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.",
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AU - Ragel, Brian T.

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AU - Gillespie, David L.

AU - Prescott, Stephen M.

AU - Couldwell, William T.

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N2 - 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.

AB - 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.

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KW - In vivo

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