Active Targeting of P-Selectin by Fucoidan Modulates the Molecular Profiling of Metastasis in Docetaxel-Resistant Prostate Cancer

• Published in: Marine drugs Vol. 20; no. 9; p. 542
• Main Authors: Ho, Chang-Hsun, Chen, Mei-Lin, Huang, Hau-Lun, Lai, Chih-Jen, Liu, Chih-Hsin, Chuu, Chih-Pin, Lin, Yu-Hsin
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23.08.2022; MDPI
• Subjects: ABC transporters; Androgens; Anticancer properties; Biological activity; Cancer; Cancer therapies; Castration; Cell migration; Cells; Chemotherapy; Combined treatment; Cyclooxygenase-2; Deprivation; docetaxel resistant; Drug resistance; Endothelium; Fucoidan; Hormones; Interleukin 1 receptors; Ligands; Metastases; Metastasis; metastasis-inhibiting signaling pathway; Motility; NF-κB protein; P-selectin; Patients; Prostate cancer; Protein expression; Proteins; Signal transduction; Synergistic effect; synergistic effects; Tumors
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20090542

The standard of care for prostate cancer (PCa) is androgen deprivation therapy (ADT). Although hormone-sensitive PCa is curable by ADT, most conditions progress to castration-resistant prostate cancer (CRPCa) and metastatic CRPCa (mCRPCa). Front-line docetaxel has been administered to patients with CRPCa and mCRPCa. Nevertheless, docetaxel resistance after half a year of therapy has emerged as an urgent clinical concern in patients with CRPCa and mCRPCa. We verified the mechanism by which docetaxel-resistant PCa cells (DU/DX50) exhibited significant cell migration and expression of malignant tumor-related proteins. Our study shows that the biological activity of fucoidan has an important application for docetaxel-resistant PCa cells, inhibiting IL-1R by binding to P-selectin and reducing the expression levels of NF-κB p50 and Cox2 in this metastasis-inhibiting signaling pathway. Furthermore, the combined treatment of fucoidan and docetaxel showed significant anticancer and synergistic effects on the viability of DU/DX50 cells, which is relevant for overcoming the current limitations and improving treatment outcomes. Overall, fucoidan-based combination chemotherapy may exert beneficial effects and facilitate the treatment of docetaxel-resistant PCa.