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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

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Notch1 is associated with the multidrug resistance of hypoxic osteosarcoma by regulating MRP1 gene expression

C Li, D Guo, B Tang

    Neoplasma
    |July 30, 2016
    PubMed

    Insights

    Hypoxia enhances osteosarcoma cell growth and drug resistance by upregulating Notch1 signaling. Inhibiting Notch1 with siRNA reduces proliferation and sensitizes cells to chemotherapy by downregulating multidrug resistance protein-1 (MRP1).

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cell Biology

    Background:

    • Hypoxia and Notch signaling are implicated in tumor progression and drug resistance.
    • The specific roles of hypoxia and Notch signaling in osteosarcoma (OS) cell proliferation and drug resistance require further elucidation.

    Purpose of the Study:

    • To investigate the molecular mechanisms of hypoxia and Notch1 signaling in osteosarcoma cell proliferation and drug resistance.
    • To evaluate the effect of inhibiting the Notch1 pathway using Notch1 small interference RNA (siRNA) on human MG-63 OS cells under hypoxic conditions.

    Main Methods:

    • Culturing human MG-63 osteosarcoma cells under hypoxic conditions.
    • Utilizing Notch1 siRNA to inhibit the Notch1 signaling pathway.
    • Assessing cell proliferation, apoptosis, cell cycle, and expression of HIF-1α, Notch1, and multidrug resistance protein-1 (MRP1) via Western blot analysis.

    Main Results:

    • Hypoxia promoted osteosarcoma cell proliferation, induced cell cycle transition (G0/G1-S-G2/M), and increased multidrug resistance.
    • Hypoxia led to increased expression of HIF-1α, Notch1, and MRP1 in osteosarcoma cells.
    • Notch1 siRNA significantly inhibited proliferation, enhanced apoptosis in hypoxic osteosarcoma cells, and sensitized them to multidrug treatment by downregulating MRP1.

    Conclusions:

    • Notch signaling is upregulated in human osteosarcoma cells under hypoxia.
    • Notch1 inhibition represents a potential therapeutic strategy to overcome chemoresistance in hypoxic osteosarcoma by regulating MRP1 gene expression.
    Keywords:
    HIF-1αNotch1hypoxiamultidrug resistanceosteosarcoma.

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