title: Knocking Down TMPRSS2-ERG Fusion Oncogene by siRNA Could be an Alternative Treatment to Flutamide.
abstract: Our purpose was to develop a new pharmacological approach for the treatment of prostate cancer (PCa), the most common neoplasia in men. Recently, we developed siRNA against the fusion oncogene TMPRSS2-ERG found in 50% of patients and showed an antitumoral activity in animal model. Herein, we want to compare or combine the developed siRNA to flutamide (FLU), one of the gold-standard treatment of PCa. Therefore, concomitant or subsequent association of FLU to siRNA TMPRSS2-ERG was performed in VCaP cells and in SCID mice bearing xenografted VCaP tumors. ERG, androgen receptor, cleaved-caspase-3 as well as phase 1 and 2 drug-metabolizing enzymes were investigated within tumors. We observed similar results in terms of TMPRSS2-ERG knock-down and cell viability impairment for all distinct schedules of administration. The association of siRNA TMPRSS2-ERG-squalene nanoparticles with flutamide displayed similar tumor growth inhibition as mice treated with siRNA TMPRSS2-ERG-squalene nanoparticles alone and was paralleled with modification of expression of ERG, androgen receptor, and cleaved-caspase-3. Phase 1 and 2 enzymes were essentially affected by FLU and reverted when combined with squalenoylated siRNA. In conclusion, these results confirm the therapeutic effectiveness of squalenoyl siRNA nanomedicine for PCa based on siRNA TMPRSS2-ERG.
authors.affiliation: Vectorology and Anticancer Therapies, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Urbinati
authors.affiliation: INSERM UMR-S1147, 45 rue des Saints Pères, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: de Waziers
authors.affiliation: Vectorology and Anticancer Therapies, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Mateja
authors.initials: M
authors.lastname: Slamiç
authors.affiliation: Vectorology and Anticancer Therapies, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Tobias
authors.initials: T
authors.lastname: Foussignière
authors.affiliation: Vectorology and Anticancer Therapies, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France.|University College of Veterinary and Animal Sciences, Bahawalpur, Pakistan.
authors.forename: Hafiz M
authors.initials: HM
authors.lastname: Ali
authors.affiliation: Institut Galien, UMR 8612 CNRS, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.affiliation: Institut Galien, UMR 8612 CNRS, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.affiliation: Vectorology and Anticancer Therapies, UMR 8203, CNRS, Univ. Paris-Sud, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Massaad-Massade