Selinexor, a selective inhibitor of XPO-1, shows antitumor activity in rhabdomyosarcoma cell lines

Rhabdomyosarcoma (RMS) are treated with neoadjuvant chemotherapy and local therapy. In order to reduce long-term effects and to improve the prognostic parameters for high-risk RMS, alternative and individualized therapy methods are desirable. We could show that the nuclear export protein XPO-1 is overexpressed in RMS. Elevated XPO-1 prevents many tumor suppressors from performing their function. The present study investigates the effect of the XPO-1 Inhibitor Selinexor (SEL) in combination with Doxorubicin (DOX) on rhabdomyosarcoma cells.

Two RMS cell lines (RD and RH30) were used. Reduction in viability was assessed by MTT, cell cycle by flow cytometry, migration by transwell – and scratch assay, and protein expression of cell cycle proteins via Western blot.

The combination therapy results in a significant viability inhibition on RD cells compared to monotherapy with DOX. In addition, significantly decreased migration was seen in RH30 cells. Observations of the cell cycle showed G1 phase arrest upon treatment with SEL. Western blots showed upregulation of cyclin D1 under treatment with SEL.

In summary, our study shows that SEL supports the effect of DOX.

Publication History

Article published online:
17 May 2022