Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, Switzerland.
Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Int J Mol Sci. 2023 Aug 2;24(15):12338. doi: 10.3390/ijms241512338.
Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).
前列腺特异性膜抗原（PSMA）为基础的成像提高了原发性、复发性和转移性前列腺癌的检测率。然而，在某些患者中，PSMA 表面表达水平低可能会限制这种有前途的诊断工具的应用。PSMA 的药理学诱导可能有助于进一步提高 PSMA 为基础的成像的检测率。为了实现这一目标，我们测试了度他雄胺（Duta）——通常用于治疗良性前列腺增生——和洛伐他汀（Lova）——一种用于降低血脂浓度的化合物。我们旨在比较 Duta 和 Lova 对细胞增殖和 PSMA 表达的单独作用。此外，我们还测试了使用较低浓度的 Duta 和 Lova 的联合治疗是否可以进一步诱导 PSMA 表达。我们的结果表明，≤1 μM 的 Duta 和≥1 μM 的 Lova 处理可导致 LNCaP、C4-2 和 VCaP 细胞中全细胞和细胞膜表面 PSMA 表达的显著上调。与所有测试细胞系（LNCaP、C4-2 和 VCaP）中使用较高浓度的单一化合物处理相比，较低浓度的 Duta 和 Lova 的联合（0.5 μM Duta+0.5 μM Lova 或 0.5 μM Duta+1 μM Lova）进一步能够增强 PSMA 蛋白表达。
