JQ1,a Selective Inhibitor Of BRD4,suppresses Retinoblastoma Cell Growth By Inducing Cell Cycle Arrest And Apoptosis

Objective:Retinoblastoma(RB)is the most common intraocular cancer in children,and chemotherapy has been the first line treatment.However,due to the side effects of chemotherapy drugs,novel treatments must be developed.The purpose of this study is to explore whether JQ1,a selective BRD4 inhibitor,effectively inhibits the RB cells proliferation in vitro and in vivo.Methods:Firstly,the BRD4 expression in RB cells and tissues was detected using real-time PCR,western blot and immunohistochemistry.Then,MTT,soft agarose colony formation,cell cycle,apoptosis and western blot assays were used to explore the antiproliferation effect of JQ1 in vitro.The potential molecular mechanism was then explored using real-time PCR and western blot.Finally,the anti-tumor effect of JQ1 in vivo was explored using animal experiment and western blot assays.Results:1.BRD4 is overexpressed in RB cells and tissues.2.JQ1,a selective BRD4 inhibitor,effectively inhibited RB cells proliferation in vitro.3.JQ1 may arrest cell cycle by regulating Myc-P21-CDK2 and Myc-cyclin D3 /CDK6 pathways in RB cells.4.JQ1 also effectively inhibited tumor growth in vivo.Conclusion:BRD4 is highly expressed in retinoblastoma,and JQ1,a selective BRD4 inhibitor,effectively inhibited the RB proliferation in vivo and in vitro,which provides a new possibility for the treatment of retinoblastoma.