دورية أكاديمية
أعرض في EDS

Inhibition of the Wnt-β-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy.

التفاصيل البيبلوغرافية
العنوان: Inhibition of the Wnt-β-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy.
المؤلفون: Ma Y; Department of Orthopaedics, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China., Ren Y, Han EQ, Li H, Chen D, Jacobs JJ, Gitelis S, O'Keefe RJ, Konttinen YT, Yin G, Li TF
المصدر: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2013 Feb 08; Vol. 431 (2), pp. 274-9. Date of Electronic Publication: 2013 Jan 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Drug Resistance, Neoplasm*, Bone Neoplasms/*drug therapy , Osteosarcoma/*drug therapy , Receptors, Notch/*antagonists & inhibitors , Wnt Proteins/*antagonists & inhibitors , beta Catenin/*antagonists & inhibitors, Bone Neoplasms/pathology ; Cell Line, Tumor ; Hedgehog Proteins/metabolism ; Humans ; Osteosarcoma/pathology ; Receptors, Notch/metabolism ; Signal Transduction ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; beta Catenin/genetics
مستخلص: Osteosarcoma (OS) is one of the most common malignant bone tumors in early adolescence. Multi-drug chemotherapy has greatly increased the five year survival rate from 20% to 70%. However, the rate has been staggering for 30 years and the prognosis is particularly poor for patients with recurrence and metastasis. Our study aimed to investigate the role of Wnt-β-catenin, Notch and Hedgehog pathway in OS development because all these pathways are involved in skeletal development, tumorigenesis and chemoresistance. Our results showed that the major components in Wnt-β-catenin pathway, e.g. Wnt3a, β-catenin and Lef1, were consistently upregulated in human osteosarcoma cell line Saos2 cells compared to human fetal osteoblasts (hFOB), whereas the changes in the expression levels of Notch and Hh signaling molecules were not consistent. Knocking down β-catenin increased the Saos2 sensitivity to methotrexate (MTX) induced cell death. Consistently, the expression level of β-catenin protein correlated with the invasiveness of OS, as evidenced by more intensive β-catenin immunoreactivity in higher grade OS samples. Chemical inhibition of the Wnt-β-catenin signaling enhanced MTX mediated death of Saos2 cells. A synergistic effect with MTX was observed when both inhibitors for Wnt-β-catenin and Notch pathways were simultaneously used, while the addition of the Hh inhibitor did not further improve the efficacy. Our findings provide some novel insight to OS pathogenesis and lay a foundation for future application of Wnt-β-catenin and Notch inhibitors together with the currently used chemotherapeutic drugs to improve the outcome of OS treatment.
(Published by Elsevier Inc.)
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معلومات مُعتمدة: R01 AR054465 United States AR NIAMS NIH HHS; R01 AR055915 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (Hedgehog Proteins)
0 (Receptors, Notch)
0 (Wnt Proteins)
0 (beta Catenin)
تواريخ الأحداث: Date Created: 20130108 Date Completed: 20130816 Latest Revision: 20220331
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3710725
DOI: 10.1016/j.bbrc.2012.12.118
PMID: 23291185
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2104
DOI:10.1016/j.bbrc.2012.12.118