Department of Urology, University Hospital Zürich, University of Zurich, Laboratory for Urologic Oncology and Stem Cell Therapy, Zurich, Switzerland.
Department of Urology, University Hospital Zürich, University of Zurich, Laboratory for Urologic Oncology and Stem Cell Therapy, Zurich, Switzerland.
Neoplasia. 2024 Nov;57:101045. doi: 10.1016/j.neo.2024.101045. Epub 2024 Sep 5.
PSMA expression gradually increases from benign prostatic hyperplasia to adenocarcinoma of the prostate and is therefore used for the development of improved diagnostic (PSMA)-based prostate cancer imaging tools. Pharmacological induction of PSMA is therefore eminent to further improve the detection rate of PSMA-based imaging. Our previous studies have demonstrated that lovastatin (Lova) and dutasteride (Duta) are able to induce PSMA expression. However, the mechanisms by which PSMA is regulated in prostate cancer remain poorly understood. Androgen receptor (AR) and homeobox B13 (HOXB13) are the best known regulators of PSMA, hence in the present study we aimed to explore the PSMA regulation by HOXB13 and AR signaling in LNCaP and VCaP cells following treatments with Lova and Duta. Furthermore, our previous research revealed a growth arrest in prostate cancer cells after Lova, but not after Duta treatment. To understand this discrepancy, we explored the influence of Lova and Duta on well known tumor growth promoters, such as AR, the mTOR/Akt signaling pathways and Cyclin D1. Our results showed that treatment with Lova leads to a significant inhibition of the investigated tumor promoters and results in growth regression of LNCaP and VCaP cells. In contrast, Duta does not show these effects. Furthermore, we confirm the cooperative effect of HOXB13 and AR in regulating PSMA in LNCaP cells, and extend the investigations to an additional prostate cancer cell line (VCaP).
PSMA 表达水平逐渐从良性前列腺增生增加到前列腺腺癌，因此被用于开发改进的基于 PSMA 的前列腺癌诊断成像工具。因此，药理学诱导 PSMA 的表达对于进一步提高 PSMA 为基础的成像检测率是非常重要的。我们之前的研究表明，洛伐他汀（Lova）和度他雄胺（Duta）能够诱导 PSMA 的表达。然而，前列腺癌中 PSMA 调控的机制仍知之甚少。雄激素受体（AR）和同源盒 B13（HOXB13）是 PSMA 最著名的调节因子，因此在本研究中，我们旨在探讨 Lova 和 Duta 处理后 LNCaP 和 VCaP 细胞中 HOXB13 和 AR 信号对 PSMA 的调节作用。此外，我们之前的研究揭示了 Lova 处理后前列腺癌细胞的生长停滞，但 Duta 处理后没有。为了理解这种差异，我们探讨了 Lova 和 Duta 对已知的肿瘤生长促进剂的影响，如 AR、mTOR/Akt 信号通路和细胞周期蛋白 D1。我们的结果表明，Lova 处理导致研究的肿瘤促进剂的显著抑制，并导致 LNCaP 和 VCaP 细胞的生长回归。相比之下，Duta 没有显示出这些效果。此外，我们证实了 HOXB13 和 AR 在 LNCaP 细胞中协同调节 PSMA，并将研究扩展到另一个前列腺癌细胞系（VCaP）。
