Apoptosis of human melanoma cells induced by boron neutron capture therapy

Objective: To study the effect and underlying mechanism of boron neutron capture therapy (BNCT) on human melanoma cells. Methods: The situation of boronophenylalanine (BPA) uptake of human melanoma cells A375 was detected and then the boron-10 (¹⁰B) enriched cells were irradiated by an in-hospital neutron irradiator (IHNI-1). The radiation sensitivity was measured using clonogenic survival assay, the proliferation was examined by MTT assay, apoptosis was determined using flow cytometry, and the protein expression of cytochrome C in cytosol and activation of caspase-9 was detected by Western blot. Results: ¹⁰B concentration in A375 cells approached to (2.884±0.148) μg/10⁷ cells after 24 h culture with BPA, which met the requirement of BNCT. At 2.1 min after neutron radiation, the survival fraction of BNCT group was decreased to 58% of control (t = 2.964, P < 0.05). At 24 h after BNCT, the cell viability was decreased to 83% of control (t = 3.286, P < 0.05), the apoptosis ratio was (55.2±7.9)% (t = 9.754, P < 0.05), and the protein level of cytochrome C in cytosol and the activativity of caspase-9 were also enhanced (t = 7.625, 8.307, P < 0.05). Conclusions: Human melanoma cells can be killed by BNCT due to apoptosis through a mitochondrial pathway. (authors)