X‑ray-Sensitive Selenium Nanoparticles Enhance Esophageal Squamous Cell Carcinoma Radiotherapy through Activating P53/IGFBP3 Pathway by Regulating GPX2

Radiotherapy
remains a crucial treatment for esophageal squamous
cell carcinoma (ESCC), although the development of radiation resistance
and the occurrence of radiation-induced side effects pose significant
clinical challenges. Selenium (Se) has obvious antitumor effects,
but the sensitizing effect and mechanism of Se nanoparticles in ESCC
radiotherapy remain to be determined. The aim of this study was to
investigate which form of Se have superior sensitization of ESCC and
to investigate how Se nanoparticles (LNT-SeNPs) can enhance the radiosensitivity
of ESCC. Our findings indicate that LNT-SeNPs exhibit remarkable radiosensitizing
activity with a higher safety index. These nanoparticles effectively
inhibit cell growth, induce S-phase arrest, and promote apoptosis
through increased reactive oxygen species (ROS) production. Furthermore,
analysis via the GEO database revealed the correlation between the
selenoprotein GPX2 and the radiosensitivity of esophageal cancer.
Further investigations demonstrate that LNT-SeNPs suppress GPX2 expression,
leading to apoptosis in ESCC cells via the p53/IGFBP3 signaling pathway.
In conclusion, this study elucidates that LNT-SeNPs can enhance the
effectiveness of radiotherapy for esophageal cancer, providing valuable
insights into the potential use of Se-based drugs as adjunctive therapy.
These findings pave the way for future clinical applications aimed
at improving therapeutic outcomes in patients undergoing radiotherapy
for ESCC.