Seliciclib (CYC202; r-roscovitine) in combination with cytotoxic agents in human uterine sarcoma cell lines.

BACKGROUND Inhibition of cyclin-dependent kinases (CDKs) has recently emerged as an interesting approach to treat human malignancies. This was explored in human leiomyosarcoma (LMS) lines, which represent a tumour associated with poor survival, chemo-unresponsiveness and deregulation of cell cycle components. MATERIALS AND METHODS Using isobologram analysis with MTT chemosensitivity testing, the effects of the CDK inhibitor seliciclib (CYC202, R-roscovitine) when used alone or in combination with paclitaxel was studied in uterine cancer cell lines. Apoptotic endpoints were also examined via Annexin V assay using flow cytometry and Western blotting. RESULTS Overall seliciclib combined with paclitaxel proved synergistic for all cell lines. This was concomitant with an enhanced apoptotic effect and downregulation of the LAP survivin. CONCLUSION Our data support the use of seliciclib as part of combination therapy for uterine cancer.