Cellular Senescence Induced by Heavy Ion Radiation and Its Clearance by Senolytic ABT-263

The biological effects of heavy ion radiation-induced senescence in melanoma cells and the clearing effects of ABT-263 on senescent cells were investigated with two melanoma A375 and 92-1 cells after carbon ion radiation which was provided by the Heavy Ion Research Facility in Lanzhou (HIRFL). Cell senescence and apoptosis were detected by senescence-associated β-galactosidase (SA-β-Gal) staining, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Cell viability was measured by CCK-8, and the cell death level was detected by propidium iodide (PI) staining after radiation. The results showed that, at 120 h after 10 Gy carbon ion irradiation, the cell death rate did not exceed 10%, while over 80% of A375 cells and 60% of 92-1 cells showed typical senescence phenotypes, such as obvious expansion, flattening and senescence-associated β-galactosidase positivity, accompanying by a senescence-associated secretory phenotype and significantly increased GDF15 levels. ABT-263 treatment significantly induced apoptosis of senescent cells, and the proportion of dead cells at 120 h after radiation increased to 53% and 71% for A375 and 92-1 cells respectively. These results further clarify the senescence effect induced by heavy ion radiation on melanoma cells and highlight the potential of ABT-263 to promote senescent cells into apoptosis and eliminate the senescent cells.