| Targeting gastrin-releasing peptide as a new approach to treat aggressive refractory neuroblastomas. | |
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MedLine Citation:
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PMID: 21035156 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: The overall survival for neuroblastoma remains dismal, in part due to the emergence of resistance to chemotherapeutic drugs. We have demonstrated that gastrin-releasing peptide (GRP), a gut peptide secreted by neuroblastoma, acts as an autocrine growth factor. We hypothesized that knockdown of GRP will induce apoptosis in neuroblastoma cells and potentiate the cytotoxic effects of chemotherapeutic agents. METHODS: The human neuroblastoma cell lines (JF, SK-N-SH) were transfected with small interfering (si) RNA targeted at GRP. Apoptosis was assessed by DNA fragmentation assay. Immunoblotting was used to confirm molecular markers of apoptosis, and flow cytometry was performed to determine cell cycle arrest after GRP knockdown. RESULTS: siGRP resulted in an increase in apoptosis in the absence of chemotherapeutic interventions. A combination of GRP silencing and chemotherapeutic drugs resulted in enhanced apoptosis when compared to either of the treatments alone. GRP silencing led to increased expression of proapoptotic proteins, p53 and p21. CONCLUSION: Silencing of GRP induces apoptosis in neuroblastoma cells; it acts synergistically with chemotherapeutic effects of etoposide and vincristine. GRP knockdown-mediated apoptosis appears to be associated with upregulation of p53 in neuroblastoma cells. Targeting GRP may be postulated as a potential novel agent for combinational treatment to treat aggressive neuroblastomas. |
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Authors:
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Pritha Paul; Lauren A Gillory; Junghee Kang; Jingbo Qiao; Dai H Chung |
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Publication Detail:
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Type: Journal Article Date: 2010-10-29 |
Journal Detail:
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Title: Surgery Volume: 149 ISSN: 1532-7361 ISO Abbreviation: Surgery Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: United States |
Other Details:
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Languages: eng Pagination: 425-32 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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