PARP-1Expression In Human Glioma Tissues And The Effect Of The PARP-1Inhibitor BMN-673in The Treatment Of Glioma Cell Lines

Objective:To investigate the expression of PARP-1in human brain glioma tissues and malignant cell lines of astrocytomas/glioblastoma (U251/U87).Analyze the biological effects on tumor cells when give a PARP-1inhibitor BMN-673as a combination with common chemotherapeutic agents temozolomide.Methods:A quantitative RT-PCR assay was performed to analyze the mRNA level of PARP-1in tissue samples(5normal brain tissues,35tumor tissues) and cell lines(U251and U87).Culture the cell lines with PARP-1inhibitor BMN-673and TMZ, then evaluate DNA damage by comet assay, examine the cells inhibition by methed CCK-8and confirm apoptosis and cell cycle distribution by flow cytometry.Result:The PARP-1level in tumor samples was significantly high express than that in normal brain tissues (P<0.01). The level of PARP-1and pathological grades have a significant association. The mRNA expression level of PARP-1increased in glioma cells when cultured with BMN-673or/and TMZ. The comet assay detect BMN-673lead to increased DNA damage. The CCK-8assay showed BMN-673had significantly antiproliferative effects. Flow cytometry assay showe that the apoptosis was increased after BMN-673treatment and cell cycle was arrested at the G2/M phase.Conclusion:1. The mRNA expression of PARP-1in glioma tissues was significantly increased when compare with normal brain tissues (P<0.01). The level of PARP-1mRNA expression and pathological grades have a significant association.2. TMZ and BMN-673can upregulated the level of PARP-1mRNA expression in glioma cell lines U251and U87.3. BMN-673, a PARP-1inhibitor, can active at glioma U251, U87cell and cause increased DNA damage, growth inhibition and cycle arrest.