Figure 7. BMX is a driver of castration resistance in vitro and in vivo.

(A, B) VCaP cells in CSS medium were treated with BMX-IN-1 (A) or ibrutinib (B) for 5 days and counted (means ± SE, n=4). (C) VCaP cells in CSS medium were treated with 5 μM enzalutamide (ENZ), 5 μM ibrutinib (Ibr), or the combination (Combo) for 5 days (means ± SE, n=4). (D) Representative images of VCaP cells cultured for 2-3 weeks in Matrigel based 3D system with 5 μM enzalutamide, BMX-IN-1, and/or ibrutinib. (E) VCaP subcutaneous xenografts were established in ICR-SCID mice. The mice were castrated once the tumors reach 500 mm³ and then administered vehicle (n=13), ibrutinib (n=8) or BMX-IN-1 (n=8) (each at 100mg/kg/d) by i.p. injection. The results are means ± SE. (F, G) Castration resistant VCaP xenografts were established and then treated for 4 days with vehicle or 100 mg/kg/d BMX-IN-1 or ibrutinib via i.p. injection. (F) Representative sections were stained for cleaved caspase 3. (G) Biopsies prior to or post 4-day treatment were analyzed for PSA, TMPRSS2, NKX3.1 or AR mRNA expression by qRT-PCR.