Yasui H1, Imura Y1, Outani H1, Hamada KI1, Nakai T1, Yamada S1, Takenaka S1, Sasagawa S2, Araki N3, Itoh K2, Myoui A1, Yoshikawa H1, Naka N1,2.1a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
2b Department of Biology , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
3c Musculoskeletal Oncology Service , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
Abstract
Synovial sarcoma (SS) is an aggressive soft tissue tumour with poor prognosis.
Using five human SS cell lines, we examined the cytotoxic effects of trabectedin (ET-743; Yondelis®), a novel marine natural product, which was approved in Europe for the treatment of soft tissue sarcomas (STS).
The significant growth inhibitory effects were observed in all SS cell lines below nanomolar concentration of trabectedin.
Furthermore, trabectedin significantly suppressed the tumour growth in xenograft models.
Flow cytometer analysis in vitro and immunohistochemical analysis in vivo revealed its effect of cell cycle inhibition and apoptosis induction.
We also examined the expression of ERCC1, 5 and BRCA1 in SS cell lines and clinical samples, and majority of them showed highly trabectedin-sensitive pattern as previously reported in other cancers.
Our preclinical data indicated that trabectedin could be a promising therapeutic option for patients with SS.