Celecoxib inhibits STAT3 phosphorylation and suppresses cell migration and colony forming ability in rhabdomyosarcoma cells
Copyright © 2011 Elsevier Inc. All rights reserved..
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric and adolescent population. Though treatments for localized disease have reasonable long-term success rates, if disease is diffuse at diagnosis, outcomes are far poorer. Additional and/or alternative therapies are critical for improved clinical outcomes. One potentially therapeutic target is the signal transducer and activator of transcription 3 (STAT3) pathway. STAT3 has been shown to have constitutive activation in human rhabdomyosarcoma cells; thus, inhibition of STAT3 signaling may be a mechanism to induce tumor cell death. Celecoxib has been shown, by computer modeling, to bind STAT3 at the SH2 domain and competitively inhibit native peptide binding necessary for phosphorylation and subsequent propagation of the STAT3 signaling cascade. We found that celecoxib inhibits IL-6-induced and persistent STAT3 phosphorylation and inhibits cell viability in human rhabdomyosarcoma cells. We found that genes downstream of STAT3 (BCL-2, survivin, cyclin D1) were downregulated with celecoxib. Celecoxib also inhibits colony formation and cell migration. Our results suggest that, though known more commonly as a cyclooxygenase-2 (COX-2) inhibitor, celecoxib could act through the STAT3 pathway as well. More importantly, its effect on cell migration and clonogenic colony forming ability make it a potentially useful therapeutic agent for rhabdomyosarcoma, especially in metastatic disease whose clinical outcome is marginal at best with current therapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:407 |
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| Enthalten in: |
Biochemical and biophysical research communications - 407(2011), 3 vom: 15. Apr., Seite 450-5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reed, Suzanne [VerfasserIn] |
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| Links: |
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| Themen: |
Celecoxib |
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| Anmerkungen: |
Date Completed 14.07.2011 Date Revised 19.11.2015 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2011.03.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM20657665X |
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| 500 | |a Date Revised 19.11.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2011 Elsevier Inc. All rights reserved. | ||
| 520 | |a Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric and adolescent population. Though treatments for localized disease have reasonable long-term success rates, if disease is diffuse at diagnosis, outcomes are far poorer. Additional and/or alternative therapies are critical for improved clinical outcomes. One potentially therapeutic target is the signal transducer and activator of transcription 3 (STAT3) pathway. STAT3 has been shown to have constitutive activation in human rhabdomyosarcoma cells; thus, inhibition of STAT3 signaling may be a mechanism to induce tumor cell death. Celecoxib has been shown, by computer modeling, to bind STAT3 at the SH2 domain and competitively inhibit native peptide binding necessary for phosphorylation and subsequent propagation of the STAT3 signaling cascade. We found that celecoxib inhibits IL-6-induced and persistent STAT3 phosphorylation and inhibits cell viability in human rhabdomyosarcoma cells. We found that genes downstream of STAT3 (BCL-2, survivin, cyclin D1) were downregulated with celecoxib. Celecoxib also inhibits colony formation and cell migration. Our results suggest that, though known more commonly as a cyclooxygenase-2 (COX-2) inhibitor, celecoxib could act through the STAT3 pathway as well. More importantly, its effect on cell migration and clonogenic colony forming ability make it a potentially useful therapeutic agent for rhabdomyosarcoma, especially in metastatic disease whose clinical outcome is marginal at best with current therapies | ||
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| 700 | 1 | |a Lin, Jiayuh |e verfasserin |4 aut | |
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