Abstract
BACKGROUND: Synovial sarcoma (SS) is an aggressive malignant soft tissue sarcoma of undetermined tissue origin that harbors potential metastases and recurrences, leading to a poor prognosis. Polo-like kinase 1 (PLK1) is an essential member of the serine/threonine kinase family, which plays a key role in cell cycle progression and other cellular processes. Therefore, PLK1 could act as a promising target for treating various cancers, including a low incidence of sarcoma. METHODS: SS paraffin-embedded tissue samples were selected to detect the expression of PLK1 and apoptosis- and autophagy-related proteins using immunohistochemistry. We analyzed the effects of low PLK1 expression on the SS cell cycle and function using the PLK1 inhibitor BI2536 in SW982 and SSX1 cells (cells with high expression of the SYT-SSX1 fusion gene). Western blotting was used to detect the expression of PLK1 and apoptotic proteins in different groups. Finally, the antitumor effects and safety of BI2536 were evaluated using xenograft tumor experiments in nude mice. RESULTS: In SS tissues, PLK1 was overexpressed and autophagy-related proteins were expressed at low levels, leading to poor prognosis. Suppressing PLK1 expression using the PLK1 inhibitor BI2536 decreased the proliferation, migration, and invasion abilities of SW982 and SYT-SSX1 cells and promoted the expression of the apoptotic protein Bax. Meanwhile, we confirmed that SS cell apoptosis increased and G2/M cycle arrest occurred after PLK1 expression was inhibited. We found that BI2536 significantly inhibited the growth of SS-xenografted tumors in nude mice, and the expression of stem cell-related factors significantly decreased. CONCLUSION: PLK1 overexpression was closely associated with poor prognosis. Suppressing PLK1 expression significantly inhibited the growth, invasion, and migration of SS cells, promoted apoptosis, and blocked the G2/M phase of the cell cycle.