Overexpression of Oncogenic Polo-like kinase 1 Disrupt the Invasiveness, Cell Cycle and Apoptosis in Synovial Sarcoma

Background Synovial sarcoma (SS) is an aggressive malignant soft tissue sarcoma of undetermined tissue origin that harbored potential metastasis and recurrence, which lead to poor prognoses. Polo-like kinase1 (PLK1) is an essential members serine/threonine kinase, which plays a key role in cell cycle progression and other cellular processes Therefore, PLK1 could act as a promising target for the therapeutic cure of various cancers, including a low incidence of sarcoma. Methods We selected SS paraffin tissue samples to detect the expression of PLK1 and apoptosis and autophagy related proteins by immunohistochemistry. We analyzed the effects of low expression of PLK1 on SS cell cycle and function by using PLK1 inhibitor BI2536 in SW982 cells and SSX1 cells (cells with high expression of SYT-SSX1 fusion gene). Meanwhile, western blot (WB) was used to detect the expression of PLK1 and apoptosis protein in different groups. Finally, the antitumor effect and safety of BI2536 were tested in xenograft tumor experiments in nude mice. Result In SS tissues, PLK1 was overexpressed and autophagy related proteins were low-expressed, leading to poor prognosis. The inhibition of PLK1 expression by PLK1 inhibitor BI2536 decreased the proliferation, migration and invasion ability of SW982 and SYT-SSX1 cell lines, and promoted the expression of apoptotic protein Bax. Meanwhile, we confirmed that SS cells apoptosis increased and G2/M cycle arrest occurred after the expression of PLK1 was inhibited. We found that BI2536 significantly inhibited the growth of SS xenografted tumors in nude mice, and the expression of stem-related factors significantly decreased. Conclusion Overexpression of PLK1 is closely related to poor prognosis. Inhibition of PLK1 expression can significantly inhibit the growth, invasion and migration of SS cells, promote apoptosis and block the G2 / M phase of cell cycle.