Introduction External beam radiation (EBRT) and 125I seed continuous low dose rate radiation (CLDR)were used to treat patients with lung cancer.The reasons for the improved therapy of CLDR were not fully understood.We herein investigated the different direct effects of EBRT and CLDR on lung cancer cells and its related mechanisms.Methods A549 cells were exposed to different doses of EBRT and CLDR,respectively.6-MV X-ray linear accelerator was used for EBRT and 125I seeds were used for CLDR.Cell survival, death, cycle and apoptosis were detected.The related intracellular molecule alterations were determined by real-time PCR and western blotting.Results Significantly lower colony forming efficiency of A549 cells was observed after CLDR than EBRT.CLDR inhibited cell growth and induced apoptosis,G2/M arrest more efficiently than EBRT.Cyclin B1 levels were reduced by CLDR.P-H2AX (Ser139) and DNA-PKcs expression were significantly elevated in A549 cells after CLDR.Anti-apoptosis Bcl-2 protein levels in A549 ceils were significantly reduced and apoptosis-inducing Bax mRNA and protein levels were increased after CLDR.Conclusions CLDR was more efficient to inhibit A549 lung cancer cell growth than EBRT.Decreased cyclin B1 may mediate CLDR-induced G2/M arrest.The long-lasting p-H2AX activity indicates the enhanced DNA damage by CLDR.The significantly decreased Bcl-2/Bax ratio induced by CLDR may contribute to the increased cell death of A549.Thus, the improved inhibition of CLDR on lung cancer cell growth may be mediated, at least partially, by the decrease Bcl2/Bax ratio and cyclin B 1-related G2/M arrest.