The HDAC Inhibitor OBP-801 Suppresses the Growth of Myxofibrosarcoma Cells.

PURPOSE:Myxofibrosarcoma is characterized by a high rate of recurrence after surgery. Since myxofibrosarcoma is refractory to conventional cytotoxic chemotherapy, the established radical treatment is primary wide resection. The effects of histone deacetylase (HDAC) inhibitors on myxofibrosarcoma have not yet been investigated. Therefore, the main purpose of the present study was to examine the effects of a HDAC inhibitor on myxofibrosarcoma.METHODS:The effects of the HDAC inhibitor OBP-801 on human myxofibrosarcoma cells were examined using cell viability assay, flow cytometric analysis of the cell cycle and apoptosis, and Western blotting. The effects of combinations of OBP-801 with pazopanib or Akt-mTOR inhibitors were also investigated using cell viability assay.RESULTS:OBP-801 inhibited the growth of myxofibrosarcoma NMFH-1 and NMFH-2 cells. It also induced cell cycle arrest at the G2 phase and apoptosis in both cell lines. The inhibitory effects of pazopanib and Akt-mTOR inhibitors on the growth of myxofibrosarcoma cells were enhanced by the combination with OBP-801.CONCLUSIONS:The present results demonstrated that OBP-801 exerted therapeutic effects in myxofibrosarcoma in both single and concomitant administrations. Therefore, OBP-801 has potential as a novel treatment for myxofibrosarcoma.