Abstract: Objective To investigate the effect of metformin（DMBG）on radiosensitivity of rectal cancer cells and its possible mechanism. Methods  Rectal cancer SW1463 cells were cultured in vitro，control group，DMBG group，radiation group and metformin combined radiation group（DMBG+radiation group） were set up，a nude mouse xenograft model was also established. MTT assay and colony assay were used to detect cell ability of different concentrations（5，10，20，40，80 mmol/L） of DMBG on SW1463 cells. Flow cytometry was used to assess the apoptosis and cell cycle. The expression of DNA damage protein γ- H2AX and DNA repair protein DNA-PK were detected by Western Blot，The weight and volume of transplanted tumors were tested，the tumor inhibition rate was calculated，and the tumor growth curve was drawn. Results Different concentrations（5，10，20，40，80 mmol/L）of DMBG inhibited the ability of SW1463 cells（F=43.283，P=0.021）. The cell ability of DMBG+radiation group under different radiation doses（2，4，6，8 Gy） was lower than that of DMBG group and radiation group（P<0.05），while the apoptosis rate was significantly higher than that of DMBG group and radiation group ［（63.32±6.15） % vs （16.19±4.38） %，P<0.05；（63.32±6.15） % vs （17.24±5.17）%，P<0.05］. DMBG+ radiation group increased the proportion of G2 /M phase cells to（61.50±5.25） %，while the proportion of cells in G0/G1 phase decreased to （17.36±3.17） %，and the expression of γ-H2AX protein was up-regulated，the expression of DNA-PK protein was down-regulated，which were statistically significant compared with  the DMBG group and radiation group（P<0.05）. The volume and weight of the nude mice were significantly reduced，and the tumor inhibition rate was significantly higher than that of DMBG group and radiation group ［（68.51±2.58）% vs （20.74±2.61）%，P<0.05；（68.51±2.58）% vs （31.52±3.43）%，P<0.05］. Conclusions DMBG has radiosensitizing effect on rectal cancer SW1463 cells and its xenografts in nude mice. The combination of metformin and radiotherapy may change the cell cycle distribution and inhibit the ability of DNA damage and repair.

Key words: Rectal cancer, Metformin, Radiotherapy sensitivity, Nude mouse, Xenograft model, Cell Cycle, DNA damage, DNA repair