Fig 6.

CDK overexpression is sufficient to drive enzalutamide resistance. (A) Schematic diagram of engineering CDK4/6-overexpressing LnCAP cells and the subsequent experimental determination of enzalutamide sensitivity. (B) CDK4/6-overexpressing androgen-sensitive LnCAP cells continue to proliferate when cultured in androgen-free media (charcoal-stripped serum [CSS]) and enzalutamide 2.5 μM. The same treatment negatively impacted luciferase control–expressing LnCAP cells. The resistant phenotype was ablated when additional CDK4/6 inhibitors, palbociclib or ribociclib, were supplemented with androgen-deprivation and enzalutamide treatment. The average of three experiments is plotted and error bars represent standard deviation. (*) Overexpression of a gene led to a significant difference compared with luciferase control cells. (†) Cell-cycle inhibitor treatment led to a significant reduction of proliferation (P < .005, two-tailed t test).