Effect of lithium chloride on proliferation and apoptosis of ovarian cancer cell

OBJECTIVE:To investigate the influence of LiCl on proliferation and apoptosis in human ovarian cancer cell and the possible mechanism.METHODS:SKOV3cells were treated with 20mmol/L(A group),40mmol/L(B group) and 60mmol/L(C group)LiCl separately.The growth inhibitory effects were evaluated by CCK8assay.Cell cycle and apoptosis were observed by flow cytometry.Western blot was used to detect the expressions of proteins GSK-3β,p-GSK-3β and MAD2.RESULTS:The proliferation of SKOV3cells was inhibited by LiCl.The proliferative activities were decreased to(80.64±1.06)%for A group,(57.18±1.56)%for B group,(43.18±6.12)%for C group respectively after treated with LiCl for 48h(compared to the A group,P=0.001for B group and P0.001for C group).The proliferative activities were decreased to(75.12±9.35)%for 24hgroup,(57.18±1.56)%for 48hgroup,(35.36±1.00)%and for 72h group after treated with B group(compared to the 24hgroup,Pvalues were 0.158for 48hgroup and 0.036for 72h group).LiCl could inhibit the proliferation of SKOV3cells in a time-and dose-dependent manner.Treatment of LiCl for 96hinduced apoptosis of SKOV3cells and the apoptosis rates were increased to(7.82±0.87)% for A group,(21.09±1.57)%for B group,(27.83±0.47)%for C group compared with the control group(P=0.037for A group, P0.001for B group and C group).After treated with the different concentrations above for 48h,the percents of G2 /M phase were increased from(10.23±1.50)% of the control to(19.9±4.16)% for A group,(30.29±0.51)% for B group,(39.32±1.11)%for C group(Pvalues were 0.352for A group,0.045for B group and 0.009for C group).Flow cytometry revealed that the SKOV3cells were arrested in G2/M phase.LiCl treatment for 48hcould also up-regulate the expression level of p-GSK-3βas well as MAD2while the expression of total GSK-3βand was not change.The expression levels of p-GSK-3βwere(54.39±2.75)% for A group,(72.39±2.89)% for B group,(86.57±2.52)% for C group(Pvalues were 0.019for A group,0.009for B group and 0.005for C group)and the expression levels of MAD2were(52.29±1.34)%for A group,(58.35±1.36)%for B group,(72.07±2.93)%for C group(Pvalues were 0.041for A group,0.03for B group and 0.006for C group).CONCLUSION:LiCl can inhibit the proliferation and induce apoptosis of ovarian cancer SKOV3cells;these effects are probably mediated by up-regulating the expression of MAD2,enhancing the function of the mitotic checkpoint and leading to G2/M phase arrest ultimately.