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.