Abstract 3439: Study on the mechanism of sesamin inhibiting the malignant metastasis of prostate cancer

Abstract Purpose: Prostate cancer (PCa), a malignant tumor of the urinary tract, is one of the most common cancers in men. PCa tends to metastasize to bones and lymph nodes, resulting in increased mortality. Sasamin is a plant compound extracted from sesame seeds. Some studies suggest that sesame lignans may have the potential for antioxidative, anti-inflammatory, and anti-tumor effects. Here, we aim to investigate the inhibitory effects of sesamin on the invasiveness of PCa cells in vitro and tumor progression in vivo. Materials and Methods: Human PCa cell lines DU145 and PC-3 were obtained from the Bioresource Collection and Research Center (BCRC). Cell survival was detected by Colony formation assay. Wound healing assay, Anoikis assay and Transwell migration/invasion assay were performed to analyze cell aggressiveness. The subcutaneous tumor model was performed to study the inhibition of tumor growth by sesamin treatment. The levels of ADAM9, PD-L1 and Ki67 protein expression in tumor tissues were detected by immunohistochemistry (IHC) staining. Results: Firstly, PCa cells were treated with different concentrations of sesamin, revealing a dose-dependent inhibition of both cell survival rate and proliferative ability. The co-administration of sesamin with a chemotherapeutic drug (docetaxel & cabazitaxel) enhances chemosensitivity in PCa cells. Next, we found that sesamin inhibits cell motility, invasion, and anoikis resistance via ADAM9 down-regulation through the JNK and c-Jun signaling pathway in PCa cells. Interestingly, sesamin can reduce ADAM9-mediated cleavage of membrane-bound PD-L1 (mPD-L1) into its soluble form, thereby inhibiting immune escape in PCa. Moreover, subcutaneous injection of PCa cells in mice, followed by twice-weekly intraperitoneal injection of sesamin, resulted in tumor growth inhibition. IHC staining of mice tumor tissues revealed a decrease in the levels of ADAM9 and Ki67 expression, and an increase in mPD-L1 expression in the sesamin-treated group compared to the non-treated group. Conclusion: These results suggest that sesamin exhibits inhibitory effects on cell proliferation, migration, invasion, anoikis resistance, and immune escape in vitro, as well as tumor growth in vivo. The strategy of co-administration of sesamin can benefit clinical chemotherapy treatment, highlighting the potential of sesamin as an adjunctive treatment in PCa. Citation Format: Yen Chen Chen, An-Chen Chang, Chih-Hsin Tang, Thomas I-Sheng Hwang. Study on the mechanism of sesamin inhibiting the malignant metastasis of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3439.