Involvement of Cdc25c in Cell Cycle Alteration of a Radioresistant Lung Cancer Cell Line Established with Fractionated Ionizing Radiation

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricatesequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responsesand eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancercell line, A549R , by exposing the parental A549 cells to repeated γ-ray irradiation with a total dose of 60 Gy.The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused onexamination of the cell cycle distribution between A549 and A549R and found that the proportion of cells inthe radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 andA549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested thatG2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore thepossible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteinswhich orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied bythe decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a,determines the radioresistance of cells.