Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma

• Published in: Anticancer research 2019-12, Vol.39 (12), p.6661-6671
• Main Authors: Chen, Kuan-Hao, Lai, Zih-Yin, Li, Ding-Yu, Lin, Yu-Chuan, Chou, Fong-In, Chuang, Yung-Jen
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis Regulatory Proteins - metabolism; Boric acid; Boric Acids - pharmacokinetics; Boric Acids - therapeutic use; Boron; Boron Neutron Capture Therapy - methods; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - radiotherapy; Caspase 3 - metabolism; Cell Line, Tumor; Cell survival; Cell Survival - radiation effects; Damage; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA End-Joining Repair; DNA Repair; DNA-Binding Proteins - metabolism; Enzyme Activation; Gene expression; Hepatocellular carcinoma; Histones - metabolism; Homologous recombination; Homology; Humans; In vitro methods and tests; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - radiotherapy; Neutrons; Nuclear capture; Radiation-Sensitizing Agents - pharmacokinetics; Radiation-Sensitizing Agents - therapeutic use; Radiosensitizers; Recombinational DNA Repair; Therapy; Tumor cells
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13881

Boron neutron capture therapy (BNCT) selectively kills tumor cells while sparing adjacent normal cells. Boric acid (BA)-mediated BNCT showed therapeutic efficacy in treating hepatocellular carcinoma (HCC) in vivo. However, DNA damage and corresponding responses induced by BA-mediated BNCT remained unclear. This study aimed to investigate whether BA-mediated BNCT induced DNA double-strand breaks (DSBs) and to explore DNA damage responses in vitro. Huh7 Human HCC cells were treated with BA and irradiated with neutrons during BA-BNCT. Cell survival and DNA DSBs were examined by clonogenic assay and expression of phosphorylated H2A histone family member X (γH2AX), respectively. The DNA damage response was explored by determining the expression levels of DNA repair- and apoptosis-associated proteins and conducting a cell-cycle analysis. DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G /M arrest and apoptosis in HCC. Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC.