Abstract
PurposeTo determine the biological effectiveness of single, fractionated and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the cellular mechanisms.Materials and methodsThe CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h. Three groups were employed: single dose radiation group (SDR), fractionated dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR). Four radiation doses 2, 4, 6 and 8Gy were chosen and cells without irradiation as the control. The responses of CL187 cells to distinct modes of radiation were evaluated by the colony-forming assay, cell cycle progression as well as apoptosis analysis. In addition, we detected the expression patterns of DNA-PKcs, Ku70 and Ku80 by Western blotting.ResultsThe relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42. 48 hrs after 4Gy irradiation, the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p = 0.026), so as the FDR and CLDR groups (p = 0.005). 48 hrs after 4Gy irradiation, the early apoptotic rate of CLDR group was remarkably higher than SDR and FDR groups (CLDR vs. SDR, p = 0.001; CLDR vs. FDR, p = 0.02), whereas the late apoptotic rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs. SDR, p = 0.004; CLDR vs. FDR, p = 0.007). Moreover, DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups.ConclusionsCompared with the X-ray high dose rate irradiation, 125I seeds CLDR showed more effective induction of cell apoptosis and G2/M cell cycle arrest. Furthermore, 125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression.
Highlights
Colorectal cancer is one of the leading causes of death in the world, and more than 170,000 new patients are diagnosed in China each year
continuous low dose rate radiation (CLDR) inhibited survival of CL187 cells more efficiently than single dose radiation (SDR) and fractionated dose radiation (FDR) We firstly determined the effect of CLDR on CL187 cell survival
In order to evaluate the direct effects of SDR, FDR and CLDR on cell survival and cell death, we counted the total cell number and dead cell number 24 and 48 hrs after irradiation
Summary
Colorectal cancer is one of the leading causes of death in the world, and more than 170,000 new patients are diagnosed in China each year. Once the rectal cancer recurred, regular treating strategies such as operation, chemotherapy and external beam radiotherapy failed to achieve appreciative outcomes [1,2]. For those patients who could not receive an operation and re-. The aim of the present study is to determine the direct biological effectiveness of single dose radiation (SDR), fractionated dose radiation (FDR) and continuous low dose rate radiation (CLDR) on human colorectal cancer cell line CL187 cultured in vitro, and we aimed to unravel the underlying cellular and molecular mechanisms behind distinct modes of irradiation
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