XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors
- 1University Clinics, Bonn University
Abstract
Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. Despite high cure rates with cisplatin-based chemotherapy, resistance and long-term toxicities remain clinical challenges in TGCTs. Selinexor, an FDA-approved XPO1 inhibitor, has demonstrated anti-tumor activity in other cancers, but its potential in TGCTs remains unknown. Objective: We investigated the antitumor effects of selinexor in TGCT cell lines. Materials and methods: XPO1 RNA expression, protein abundance and localization were evaluated by immunohistochemistry in TGCT tissue microarrays and non-neoplastic testicular tissues, and by meta-analysis of publicly available gene-expression microarray datasets from normal testis, primary TGCT specimens as well as TGCT cell lines. Selinexor effects on cell viability, cell-cycle distribution and apoptosis were evaluated using XTT assay and flow cytometry. p53 and p21 expression and localization were analyzed by Western blotting and Immunofluorescence. Results: XPO1 expression was heterogeneous across normal testis, TGCT tissues and cell lines. Yet, selinexor reduced TGCT cell viability and induced G1 or G2/M cell-cycle arrest, apoptosis, increased total p53 and p21 protein levels, and their nuclear accumulation. Of note, control fibroblast exhibited limited sensitivity to selinexor. Discussion and conclusion: Our findings demonstrate that inhibition of XPO1 with selinexor might be potential therapeutic strategy for TGCTs.
Related
- Fisetin Induces Apoptosis and Inhibits Migration of Melanoma Cells by Suppressing Glycolytic Metabolism via PKM2 Inhibition.
- The Toxic Effects and Mechanism of Acetamiprid Exposure on Testicular Tissue: ALKBH5 Regulates m⁶A Modification to Affect PI3K-AKT-Mediated Apoptosis.
- In vivo Nupr1 regulates oxidative stress–endoplasmic reticulum stress crosstalk and mitochondria-dependent apoptosis in varicocele-related testicular injury
- Sulfated polysaccharides from Sargassum swartzii ameliorates glucose and lipid metabolism and enhance fertility potential by reducing testicular apoptosis and oxidative stress in diabetic mice
- Mitochondrial transplantation attenuates apoptosis and improves spermatogenic function following testicular torsion-detorsion injury in rats.
BibTeX
@misc{islam2026xpo1,
title = {{XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors}},
author = {R. Islam and A. Wladhaus and I. Bollen and L. Descher and A. Shalan and V. A. A. Balde and A. Liesen and A. Kovacevic and G. E. Merges and G. Kristiansen and H. Schorle},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.750914},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.750914v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors
AU - R. Islam
AU - A. Wladhaus
AU - I. Bollen
AU - L. Descher
AU - A. Shalan
AU - V. A. A. Balde
AU - A. Liesen
AU - A. Kovacevic
AU - G. E. Merges
AU - G. Kristiansen
AU - H. Schorle
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.750914
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.750914v1
AB - Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. Despite high cure rates with cisplatin-based chemotherapy, resistance and long-term toxicities remain clinical challenges in TGCTs. Selinexor, an FDA-approved XPO1 inhibitor, has demonstrated anti-tumor activity in other cancers, but its potential in TGCTs remains unknown. Objective: We investigated the antitumor effects of selinexor in TGCT cell lines. Materials and methods: XPO1 RNA expression, protein abundance and localization were evaluated by immunohistochemistry in TGCT tissue microarrays and non-neoplastic testicular tissues, and by meta-analysis of publicly available gene-expression microarray datasets from normal testis, primary TGCT specimens as well as TGCT cell lines. Selinexor effects on cell viability, cell-cycle distribution and apoptosis were evaluated using XTT assay and flow cytometry. p53 and p21 expression and localization were analyzed by Western blotting and Immunofluorescence. Results: XPO1 expression was heterogeneous across normal testis, TGCT tissues and cell lines. Yet, selinexor reduced TGCT cell viability and induced G1 or G2/M cell-cycle arrest, apoptosis, increased total p53 and p21 protein levels, and their nuclear accumulation. Of note, control fibroblast exhibited limited sensitivity to selinexor. Discussion and conclusion: Our findings demonstrate that inhibition of XPO1 with selinexor might be potential therapeutic strategy for TGCTs.
ER -