Presentation Authors: Alexander Tamalunas*, Cora Sauckel, Anna Ciotkowska, Beata Rutz, Christian G. Stief, Christian Gratzke, Martin Hennenberg, Munich, Germany
Introduction: Medical treatment in benign prostatic hyperplasia (BPH) includes reduction of prostate size to prevent disease progression, complications, and surgery, and also reduction of prostate smooth muscle tone for rapid relieve of lower urinary tract symptoms (LUTS). Combination therapies are still required to target both at once. However, current medications are insufficient, causing high rates of patient non-compliance due to an unfavourable balance between side effects and efficacy, with discontinuation rates peaking up to 90% for combination therapies. Here, we investigated the effect of lenalidomide on cellular functions including cytoskeletal organization and growth of prostate stromal cells.
Methods: Experiments were carried out in an immortalized line of cultured human prostate stromal cells (WPMY-1). Cytoskeletal organization was visualized by phalloidin staining, while cell growth was assessed using an EdU and Colony formation assay. Cytotoxicity was addressed using CCK8.
Results: Lenalidomide significantly reduced the proliferation of WPMY-1 cells. This decline was concentration-dependent, with a significantly lower proliferation rate after 72 hours of incubation. Thus, proliferation was reduced after 72 h from 64% for control to 37% and 34% for 100 and 200 ÂµM, (p < 0.01 for lenalidomide vs. control, fig. 1 A and B). Also, colony formation was reduced after 168 h to 65% and 53% for 100 and 200 ÂµM, respectively (p < 0.01 for lenalidomide vs. control, fig. 2 A and B). Using CCK8, no cytotoxic effects on WPMY-1 cells occurred after 72 h. In parallel, lenalidomide induced cytoskeletal disorganization: while the cellular shape of control cells was characterized by many long and thin protrusions containing bundles of actin filaments, this structure collapsed after treatment with lenalidomide (fig. 3).
Conclusions: Lenalidomide impairs human prostate smooth muscle growth of stromal cells, without showing cytotoxic effects. This is paralleled by a breakdown of the actin cytoskeleton, which may inhibit prostate smooth muscle contraction. Urodynamic effects in vivo appear highly possible. Functional studies as well as animal models merit further consideration.