Prostate cancer is often treated by perturbing androgen receptor signalling. CACNA1D, encoding Ca_V1.3 ion channels is upregulated in prostate cancer. Here we show how hormone therapy affects CACNA1D expression and Ca_V1.3 function. Human prostate cells (LNCaP, VCaP, C4-2B, normal RWPE-1) and a tissue microarray were used. Cells were treated with anti-androgen drug, Enzalutamide (ENZ) or androgen-removal from media, mimicking androgen-deprivation therapy (ADT). Proliferation assays, qPCR, Western blot, immunofluorescence, Ca²⁺-imaging and patch-clamp electrophysiology were performed. Nifedipine, Bay K 8644 (Ca_V1.3 inhibitor, activator), mibefradil, Ni²⁺ (Ca_V3.2 inhibitors) and high K⁺ depolarising solution were employed. CACNA1D and Ca_V1.3 protein are overexpressed in prostate tumours and CACNA1D was overexpressed in androgen-sensitive prostate cancer cells. In LNCaP, ADT or ENZ increased CACNA1D time-dependently whereas total protein showed little change. Untreated LNCaP were unresponsive to depolarising high K⁺/Bay K (to activate Ca_V1.3); moreover, currents were rarely detected. ADT or ENZ-treated LNCaP exhibited nifedipine-sensitive Ca²⁺-transients; ADT-treated LNCaP exhibited mibefradil-sensitive or, occasionally, nifedipine-sensitive inward currents. CACNA1D knockdown reduced the subpopulation of treated-LNCaP with Ca_V1.3 activity. VCaP displayed nifedipine-sensitive high K⁺/Bay K transients (responding subpopulation was increased by ENZ), and Ni²⁺-sensitive currents. Hormone therapy enables depolarization/Bay K-evoked Ca²⁺-transients and detection of Ca_V1.3 and Ca_V3.2 currents. Physiological and genomic CACNA1D/Ca_V1.3 mechanisms are likely active during hormone therapy—their modulation may offer therapeutic advantage.

前列腺癌通常通过扰乱雄激素受体信号传导来治疗。编码 Ca _{V 1.3 离子通道的}CACNA1D在前列腺癌中上调。在这里，我们展示了激素疗法如何影响CACNA1D表达和 Ca _V 1.3 功能。使用人类前列腺细胞（LNCaP、VCaP、C4-2B、正常 RWPE-1）和组织微阵列。用抗雄激素药物恩杂鲁胺 (ENZ) 或从培养基中去除雄激素，模拟雄激素剥夺疗法 (ADT) 处理细胞。进行了增殖测定、qPCR、蛋白质印迹、免疫荧光、Ca ²⁺成像和膜片钳电生理学。硝苯地平、Bay K 8644（Ca _V 1.3 抑制剂、激活剂）、米贝拉地尔、Ni ²⁺（Ca使用_V 3.2 抑制剂）和高 K ^{+去极化溶液。}CACNA1D和 Ca _V 1.3 蛋白在前列腺肿瘤中过表达，CACNA1D 在雄激素敏感的前列腺癌细胞中过表达。在 LNCaP 中，ADT 或 ENZ 随时间增加CACNA1D，而总蛋白几乎没有变化。^{未经处理的 LNCaP 对去极化高 K +} /Bay K（激活 Ca _V 1.3）没有反应；此外，很少检测到电流。ADT 或 ENZ 处理的 LNCaP 表现出对硝苯地平敏感的 Ca ^{2+ -}瞬变；ADT 处理的 LNCaP 表现出对米贝拉地尔敏感或偶尔对硝苯地平敏感的内向电流。CACNA1D敲低减少了具有 Ca _V 1.3 活性的已处理 LNCaP 亚群。VCaP 显示出对硝苯地平敏感的高 K ⁺ /Bay K 瞬变（响应亚群因 ENZ 而增加）和 Ni ²⁺敏感电流。激素疗法可实现去极化/Bay K 诱发的 Ca ²⁺ -瞬变和 Ca _V 1.3 和 Ca _V 3.2 电流的检测。生理和基因组CACNA1D /Ca _V 1.3 机制可能在激素治疗期间活跃——它们的调节可能提供治疗优势。