Evidence for a Potential Context-Dependent Dual Role of Eb Peptide of IGF-1Eb in Cancer Cell Survival and Adaptation to UV Stress

The IGF-1Eb isoform has been proposed as a stress-responsive variant of IGF-1, yet its significance in cancer remains unclear. This investigation aims to clarify its role across breast, prostate and liver cancer cell lines and determine whether its loss or supplementation is associated with alterations in cellular behavior and stress adaptation. Eb expression was modulated through targeted silencing and exogenous peptide addition. Cellular responses were evaluated under normal conditions and UV stress using proliferation, viability and rescue experiments, wound healing, immunofluorescence for Eb-knockdown confirmation, qRT-PCR, Annexin V/PI apoptosis, and PI cell-cycle evaluation. Across six cancer cell lines, Eb peptide given before UV stress was associated with partial protective effects, whereas post-UV treatment was associated with improved recovery and partial restoration of proliferative capacity. The rescue effect differed by cell type, with prostate and breast cells showing the strongest responses and liver-derived lines displaying more modest improvements. Eb knockdown revealed clear cell-type-specific dependencies. PC3 cells showed markedly reduced proliferation (p < 0.01) and sharply decreased post-UV viability (p < 0.0001). HepG2 cells maintained higher growth without UV but displayed reduced recovery following UV exposure, whereas MDA-MB-231 exhibited elevated apoptosis (p < 0.05) with limited additional UV sensitivity. Eb peptide may exert a dual, timing-dependent role, supporting protection before UV damage and facilitating recovery-associated responses afterward, with its impact differing across cell lines.