Silencing of Notch3 Using shRNA driven by survivin promoter inhibits growth and promotes apoptosis of human T-cell acute lymphoblastic leukemia cells

Abstract

Background: As a highly conserved system, the activation of the Notch pathway has been implicated in the tumorigenesis of various hematologic diseases, including leukemias, lymphomas, and multiple myeloma. The Notch3 receptor is frequently expressed in T-cell acute lymphoblastic leukemia (T-ALL).

Methods: To explore its possibility as a therapeutic target for T-ALL, we investigated the effect of Notch3 silencing on Jurkat and SupT1 cells using a novel tumor-specific short hairpin RNA (shRNA) driven by survivin promoters.

Results: We found that downregulated expression of Notch3 correlated with significant apoptosis and inhibition of proliferation.

Conclusion: These facts suggest that downregulating expression of Notch3 could attenuate the Notch signaling activity in T-ALL. All these results indicate that inhibition of Notch3 expression can result in potent antitumor activity in T-ALL.