Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3.

摘要: An important drawback in the management of glioblastoma (GBM) patients is frequent relapse upon surgery and therapy. A likely explanation that conventional therapies poorly affect a small population stem-like cancer cells (glioblastoma stem cells, GSCs) remain capable repopulating tumour mass. Indeed, development therapeutic strategies able to hit GSCs while reducing burden has become an challenge increase patient’s survival. The signal transducer activator transcription-3 (STAT3) been reported play pivotal role maintaining initiating capacity GSC population. Therefore, order impair renewal propagation PDGFRβ-expressing population, here we took advantage aptamer–siRNA chimera (AsiC), named Gint4.T-STAT3, previously have shown efficiently antagonize STAT3 subcutaneous PDGFRβ-positive GBM xenografts. We demonstrate aptamer conjugate effectively specifically prevent patient-derived function expansion. Moreover, because potential using miR-10b inhibitors broad expression Axl receptor GBM, used GL21.T anti-Axl as targeting moiety for anti-miR-10b, showing that, combination with AsiC, aptamer–miR-10b antagonist treatment further enhances inhibition sphere formation. Our results highlight use combined approach targeted RNA therapeutics inhibit dissemination relapse.