Abstract: Objective Toexplore the lethal action and possible mechanism of RI-1, a RAD51 inhibitor, on MSH2 deficient colorectal cancer cells. Method The expression of MSH2 protein level was assessedby Western blot , andthe sensibility of human colorectal cancer cells to RI-1 （10, 20, 30, 40and 50 μmol/L）was measuredby MTT method. Lentivirus vectorsMSH2-shRNA and Neg-shRNA (negative control) were constructed and transfected into HT29 cell. Apoptosis and DNA damage of cellstreated with RI-1（40 μmol/L）were detectedby flow cytometryand Single cell gel electrophoresis respectively. In addition, the formation of γ-H2AX foci was analyzed by immunofluorescence. Results Compared with control, MSH2-deficientHCT8 cellshad obviously apoptosis（P<0.01）；in HCT8 and HT29Shmsh2 cells,tail DNA%, tail length, tail moment and olive tailmomentweremarkedly increased（P<0.05）,and the number ofγ-H2AX focuswere increased（P<0.01）.Conclusions RAD51 inhibitor RI-1 selectivelykilled MSH2 deficient colorectal cancer cells by increasing DNA damage.

Key words: Key words: RI-1 colorectal cancer cell RAD51 MSH2