Anti-GPC3 Antibody-Conjugated BEZ235 Loaded Polymeric Nanoparticles (Ab-Bez235-np) Enhances Radiosensitivity in Hepatocellular Carcinoma Cells by Inhibition of DNA Double-Strand Break Repair.
Journal of biomedical nanotechnology(2020)
Abstract
AIM:To assess AB-BEZ235-NP potential as a radio-sensitizer in hepatocellular carcinoma models.METHOD:By comparing hepatocellular carcinoma cell with simple radiation or combined AB-BEZ235-NP therapy, the HCC apoptosis and self-repair level have significant differences in mortality rates and cell migration abilities.RESULTS:Cell proliferation and DNA damage increased by pretreatment with AB-BEZ235-NP after irradiation; further studies on the repair pathway indicated that AB-BEZ235-NP inhibited the important pathway of DSB repair. Our results further show that AB-BEZ235-NP significantly inhibits the phosphorylation of the canonical protein, γ-H2AX, in the NHEJ DSB repair pathway and Serine Protein Kinase (SPK) ATM, and TP53-Binding Protein one. More importantly, AB-BEZ235-NP increased the mount of mean γ-H2AX Foci in irradiated cells, indicating that AB-BEZ235-NP can selectively inhibit DSB repair in HCC cells. Therefore, these results clearly eludicate that treatment with AB-BEZ235-NP is a potential promising therapy which can increase the radiosensitivity to HCC.
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Key words
Dactolisib (BEZ235),DNA-PKcs,ATM,Hepatocellular Carcinoma,Radiosensitivity
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