Effects of Combined AKT Inhibitor NTQ1062 and PARP Inhibitor Olaparib in Ovarian Cancer Cells
Objective:To investigate the synergism and mechanism of AKT inhibitor NTQ1062 and PARP inhibitor Olaparib in ovarian cancer cells.Methods:The effects of NTQ1062 and Olaparib on the proliferation of three ovarian cancer cell lines(OVCAR-3,TOV-21G,A2780)were studied.The expression of proteins related to PI3K/AKT signaling pathway,homologous recombination repair and DNA damage re-pair were detected by Western blot.Apoptosis were detected by Annexin V-FITC double staining.Results:The results showed that NTQ1062 had strong inhibitory effects on proliferation of TOV-21G and A2780 cell lines,but had a weak inhibitory effect on proliferation of OVCAR-3 cells,and the combined treatment could increase the proliferation inhibition of the three ovarian cancer cell lines.In Western blot experi-ments,NTQ1062 increased the phosphorylation of AKT,inhibited the phosphorylation of S6RP,increased the expression of γH2AX protein and decreased the expression of RAD51 protein in the ovarian cancer cells,and the combination treatment had synergistic effects;Further studies found that the combination treatment decreased the expression of BRCA1 protein in TOV-21G cells,but had no significant effect on A2780 cells.In apoptosis experiments,NTQ1062 increased apoptosis and the combination treatment signifi-cantly increased the effects of apoptosis.Conclusion:NTQ1062 can inhibit OVCAR-3,TOV-21G and A2780 cell proliferation,and has synergistic effects when combined with olaparib,which may be effective in inhibiting PI3K/AKT pathway,reducing DNA damage and homologous recombination repair,decreasing BRCA1 protein expression and increasing apoptosis.This study can provide theoretical and technical basis for the clinical formulation of AKT inhibitor NTQ1062 combining with PARP inhibitor olaparib in the treatment of ovarian cancers.
万方数据
维普
