Effect and mechanism of olaparib on senescence of MCF-7 breast cancer cells
Objective To study the cellular senescence and molecular mechanism of olaparib in MCF-7 breast cancer cells.Methods The effects of olaparib on the proliferation and migration of MCF-7 cells were detected dynamically by real-time cell analysis(RTCA)technology.The effects of olaparib on the Senescence was detected by using the senescence-associated β-galactosidase(SA-β-gal).Quantitative polymerase chain reaction was used to analyze the effects of olaparib on the expression levels of genes encoding the senescence-associated factors p16,p21,C/EBP homologous protein,interleukin(IL)-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,p27,retinoblastoma gene,Ki67,and E2F1.The effects of olaparib on the expression levels of the senescence-associated proteins p21,γH2AX,pRB,cyclin D1,insulin-like growth factor binding protein 3,and Ki67 were analyzed by Western Blot.Results Olaparib inhibited the proliferation and migration and induced the senescence of MCF-7 cells.Long-term(96 h)treatment with olaparib significantly up-regulated the gene expression levels of p16,p21,p27,C/EBP homologous protein,IL-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,and retinoblastoma protein(P＜0.01)and significantly down-regulated the gene expression levels of Ki67 and E2F1(P＜0.01)in MCF-7 cells.Olaparib significantly increased protein expression levels of p21,γH2AX,and insulin-like growth factor binding protein 3 in MCF-7 cells(P＜0.01,P＜0.01,P＜0.05)and significantly decreased cyclin D1,pRB,and Ki67 levels(P＜0.05,P＜0.01,P＜0.05).Conclusions Olaparib can inhibit proliferation and migration and induce senescence in MCF-7 breast cancer cells.
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