Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma
| Autor: | Zih-Yin Lai, Fong-In Chou, Yu-Chuan Lin, Kuan-Hao Chen, Ding-Yu Li, Yung-Jen Chuang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Radiation-Sensitizing Agents Carcinoma Hepatocellular DNA End-Joining Repair DNA Repair DNA damage DNA repair Cell Survival Boron Neutron Capture Therapy Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Boric Acids In vivo Cell Line Tumor medicine Humans DNA Breaks Double-Stranded Clonogenic assay Chemistry Caspase 3 Liver Neoplasms Recombinational DNA Repair General Medicine medicine.disease Homologous Recombination Pathway DNA-Binding Proteins Enzyme Activation Oncology Apoptosis 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Apoptosis Regulatory Proteins DNA |
| Zdroj: | Anticancer research. 39(12) |
| ISSN: | 1791-7530 |
| Popis: | Background 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. Materials and methods 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. Results DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G2/M arrest and apoptosis in HCC. Conclusion Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC. |
| Databáze: | OpenAIRE |
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