Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases.

摘要: Proton beam is useful to target tumor tissue sparing normal cells by allowing precise dose only into cells. However, the cellular and molecular mechanisms which proton induces cell death are still undefined. We irradiated three different (LLC, HepG2, Molt-4) with low energy (35 MeV) spread out Bragg peak (SOBP) in vitro, investigated MTT or CCK-8 assay at 24 h after irradiation. LLC HepG2 were sensitive over 10 Gy induce apoptosis whereas Molt-4 showed rather sensitivity. Relative biological effectiveness (RBE) values for rate relative γ-ray ranged from 1.1 2.3 but 0.3 0.7 11 d irradiation colony formation assay. The typical apoptotic nuclear DNA morphological pattern was observed staining 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented not treatment of fragment By FACS analysis stained FITC-Annexin-V, early as well median fractions clearly increased treatment. beam-irradiated induced a cleavage poly (ADP-ribose) polymerase-1 (PARP-1) procaspases-3 -9. Activity caspases highly enhanced Reactive oxygen species (ROS) significantly N-acetyl cysteine pretreatment restored beam. Furthermore, p38 JNK ERK activated dominant negative mutants revived proton-induced apoptosis, suggesting that pathway may be through ROS activate apoptosis. In conclusion, our data single SOBP solid (LLC HepG2) an program induction activities.