The nuclear export inhibitor selinexor inhibits hypoxia signaling pathways and 3d spheroid growth of cancer cells

Reinhard Depping, Moritz Von Fallois, Yosef Landesman, Friederike Katharina Kosyna*

*Korrespondierende/r Autor/-in für diese Arbeit
2 Zitate (Scopus)

Abstract

Purpose: The nucleocytoplasmic transport of macromolecules is critical for both cell physiology and pathophysiology. Exportin 1 (XPO1), the major nuclear export receptor, is involved in the cellular adaptation to reduced oxygen availability by controlling the nuclear activity of the hypoxia-inducible factors (HIFs). Recently, a specific inhibitor of XPO1, selinexor (KPT-330), has been identified that inhibits nuclear export of cargo proteins by binding to the XPO1 cargo-binding pocket. Patients and methods: We used different cancer cell lines from human tissues and evaluated the physiological activity of selinexor on the hypoxia response pathway in twodimensional (2D) monolayer cell cultures in quantitative real-time (qRT)-PCR experiments and luciferase reporter gene assays. A three-dimensional (3D) tumor spheroid culture model of MCF-7 breast cancer cells was established to analyze the effect of selinexor on 3D tumor spheroid structure, formation and viability. Results: Selinexor treatment reduces HIF-transcriptional activity and expression of the HIF- 1 target gene solute carrier family 2 member 1 (SLC2A1). Moreover, 3D tumor spheroid structure, formation and viability are inhibited in response to selinexor-induced nuclear export inhibition. Conclusion: Here, we demonstrate the effect of specific XPO1-inhibition on the hypoxic response on the molecular level in 2D and 3D culture models of MCF-7 cells.

OriginalspracheEnglisch
ZeitschriftOncoTargets and Therapy
Jahrgang12
Seiten (von - bis)8387-8399
Seitenumfang13
ISSN1178-6930
DOIs
PublikationsstatusVeröffentlicht - 2019

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

Fingerprint

Untersuchen Sie die Forschungsthemen von „The nuclear export inhibitor selinexor inhibits hypoxia signaling pathways and 3d spheroid growth of cancer cells“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren