Abstract A051: The long non-coding RNA PCA3 silencing sensitizes metastatic prostate cancer cells to docetaxel

Abstract Prostate cancer (PCa) is an androgen dependent disease and is one of the most common malignancies in men with high death rate worldwide. Conventional chemotherapy with docetaxel (DTX) represents the standard first line treatment in patients with castration-resistant PCa (CRPC). Efforts are needed to improve DTX therapeutic efficacy, since drug resistance is a major clinical challenge in the management of PCa. Prostate cancer antigen 3 (PCA3) is an overexpressed prostate long non-coding RNA (lncRNA) that modulates PCa cell survival through modulating androgen receptor (AR) signaling, besides controlling the expression of key cancer-related genes. However, the contribution of PCA3 to resistance and sensitization to DTX chemotherapy has not yet been described. This study aims to investigate whether PCA3 silencing sensitizes human metastatic prostate carcinoma cell line (LNCaP) to DTX. The DTX concentration that reduces cell viability by 50% (IC50) was determined in LNCaP by MTT assay. LNCaP cells were treated with DTX in combination or not with PCA3 silencing using specific small interfering RNA (siRNA) molecules. Cell viability was evaluated by MTT and trypan blue staining exclusion assays. LNCaP cell morphology analysis was performed by phase contrast microscopy. Flow cytometry analysis was conducted to assess apoptosis index and cell cycle. In response to PCA3 silencing combined with DTX 11.8 nM treatment, the number of LNCaP cells were significantly reduced. The cells acquired a more rounded shape and there was a reduction of cell clusters and density. There was also a significantly reduction in the number of adherent cells. No significant changes in the apoptotic index nor the cell cycle distribution was observed. Our findings suggest that PCA3 silencing sensitizes metastatic PCa cells to DTX treatment, through other cellular mechanisms different from apoptosis and the cell cycle. Citation Format: Ana E G. Lemos, Isabella d S. Guimarães, Aline da Rocha d R. Matos, Luciana B. Ferreira, Etel R P. Gimba. The long non-coding RNA PCA3 silencing sensitizes metastatic prostate cancer cells to docetaxel [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A051.