Effect of boron neutron capture therapy on cell proliferation and cell cycle arrest in glioma stem cells

Abstract

Objective To study the effect and mechanism of boron neutron capture therapy (BNCT) on cell cycle procession in human glioma stem cells (GSCs) in vitro,and to analyze the difference of sensitivity for BNCT on GSCs and glioma cells.Methods Firstly,uptake of boronophenylalarine (BPA) on human GSCs SU2 and glioma cells SHG-44 was detected.Then the cells enriched boron-10 (10B) were irradiated by In-Hospital Neutron Irradiator (IHNI-1).The radiation sensitivity was measured using clonogenic survival assay.The proliferation was examined by MTT assay.The cell cycle procession was determined using flow cytometry.The protein expression of cyclin B1,CDK1 and P21[WAF1] were detected by Western blot.Results 10B concentration of SU2 and SHG-44 cells arrived at (1.76 ±0.28) and (2.50 ±0.12) μg/107cells at 24 h in 5 mMBPA.After radiation by IHNI-1,the survival fraction and viability of cells enriched 10B were decreased significantly (P ＜ 0.05 orP ＜ 0.01),compared with those of 10B-free.The BNCT sensitivity of SU2 cells was lower than that of SHG-44 cells (P ＜ 0.05).The proportion of G2/M phase of SU2 and SHG-44 cells was increased after BNCT compared with that of 10B-free(P ＜ 0.05).The protein levels of cyclin B1 and CDK1 were decreased(P ＜ 0.01),and that of P21[WAF1] was increased(P ＜ 0.01).Conclusions The BNCT sensitivity of GSCs was lower than that of glioma cells.BNCT could inhibite cell regeneration and proliferation and make G2/M to be blocked by inhibition of cell cycle protein formation. Key words: Boron neutron capture therapy; Glioma stem cells ; Cell cycle