Lenalidomide and pomalidomide inhibit growth of prostate stromal cells and human prostate smooth muscle contraction.
Lenalidomide and pomalidomide inhibit growth of prostate stromal cells and human prostate smooth muscle contraction.
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来那度胺和泊马度胺抑制前列腺基质细胞的生长和人前列腺平滑肌收缩
DOI：
10.1016/j.lfs.2021.119771
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发表时间：
2021
期刊：
影响因子：
6.1
通讯作者：
Hennenberg M
中科院分区：
文献类型：
--
作者：
Tamalunas A;Sauckel C;Ciotkowska A;Rutz B;Wang R;Huang R;Stief CG;Gratzke C;Hennenberg M
目的良性前列腺增生继发下尿路症状的药物治疗的特点是有限的疗效和明显的副作用之间的不利平衡。我们最近报道，沙利度胺减少前列腺平滑肌收缩，抑制细胞生长。与沙利度胺一样，其类似物来那度胺和泊马度胺也在临床使用。因此，我们研究了来那度胺和pomalidomide对人前列腺平滑肌收缩，细胞骨架组织，和生长相关的功能在stromal cells.Materials and MethodsProliferation的影响进行了评估EdU测定和集落形成，细胞骨架组织鬼笔环肽染色，CCK 8细胞活力，细胞凋亡和细胞死亡的流式细胞术在培养的前列腺基质细胞（WPMY-1）。用甲氧胺、去甲肾上腺素、苯肾上腺素、内皮素-1、U46619或电场刺激（EFS）在器官浴中诱导根治性前列腺切除术后的人前列腺组织收缩。平行地，肌动蛋白丝的组织在用来那度胺和泊马度胺治疗后崩溃。来那度胺和泊马度胺抑制肾上腺素能收缩和非肾上腺素能收缩以及EFS诱导的神经源性收缩。既没有减少活力，也没有增加细胞死亡或凋亡被观察到在WPMY-1 cells. SignificanceThalidomide衍生物损害人前列腺基质细胞的生长，而不显示细胞活力的减少，并在平行，抑制肾上腺素能，神经原性和非肾上腺素能收缩的肌动蛋白细胞骨架的分解。体内尿动力学效应似乎是可能的。
AimsMedical treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia is characterized by an unfavorable balance between limited efficacy and pronounced side effects. We recently reported, that thalidomide reduces prostate smooth muscle contraction and inhibits cell growth. Like thalidomide, its analogs lenalidomide and pomalidomide are also in clinical use. Therefore, we investigated the effects of lenalidomide and pomalidomide on human prostate smooth muscle contraction, cytoskeletal organization, and growth-related functions in stromal cells.Materials and methodsProliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, cell viability by CCK8, and apoptosis and cell death by flow cytometry in cultured prostate stromal cells (WPMY-1). Contractions of human prostate tissues from radical prostatectomy were induced by methoxamine, noradrenaline, phenylephrine, endothelin-1, U46619, or electric field stimulation (EFS) in an organ bath.Key findingsProliferation of WPMY-1 cells was significantly reduced by lenalidomide (5–200 μM) and pomalidomide (2.5–5 μM). In parallel, organization of actin filaments collapsed after treatment with lenalidomide and pomalidomide. Lenalidomide and pomalidomide inhibited both adrenergic contractions and non-adrenergic contractions as well as neurogenic contractions induced by EFS. Neither reduction in viability, nor increase in cell death or apoptosis was observed in WPMY-1 cells.SignificanceThalidomide-derivatives impair growth of human prostate stromal cells, without showing a decrease in cell viability and, in parallel, inhibit adrenergic, neurogenic, and non-adrenergic contractions by breakdown of the actin cytoskeleton. Urodynamic effects in vivo appear possible.
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DOI：
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