EPZ015666,a Selective PRMT5 Inhibitor With An Antitumor Effect In Retinoblastoma

Purpose:To study whether PRMT5 was up-regulated in retinoblastoma(RB),whether it promotes retinoblastoma growth,and whether PRMT5 inhibitor EPZ015666 inhibit retinoblastoma in vivo and vitro.Methods:In this study,regarding retinal epithelial cell line(ARPE-19)as controls,real-time qPCR and Western blot assay were performed to detected whether PRMT5 mRNA and protein expression were up-regulated in retinoblastoma cells(Y79,WERI-Rb-1);immunohistochemical experiments was performed to identify whether PRMT5 overexpressed in retinoblastoma tissues at the tissue level.Meantime,we made overexpression or knockdown of PRMT5 in RB cells through infection,then detected the cell proliferation ability.We treated Y79 and WERI-Rb-1 cells with various concentrations of the PRMT5 inhibitor EPZ015666(5?M,10?M,20?M,30?M).The control group was treated with an equal volume of medium containing DMSO.To detected proliferation ability of cells,A series of studies were performed: MTT assay and colony formation assay and flow cytometry.Western blot assay was used to detect the expression levels of cycle-related factors.The subcutaneous tumor formation test in nude mice was used to study the antitumor effect of the PRMT5 inhibitor in vivo.Results:1.PRMT5 was overexpressed in retinoblastoma cells.2.Overexpressed PRMT5 promoted Y79 cells proliferation and knockdown of PRMT5 suppressed WERI-Rb-1 cells proliferation.3.PRMT5 inhibitor EPZ015666 inhibits retinoblastoma cell proliferation.4.EPZ015666 regulates cell cycle related factor expression.5.EPZ015666 inhibits tumor growth in vivo.Conclusion:PRMT5 is overexpressed in RB cells,and it promotes RB growth.The PRMT5 inhibitor EPZ015666 inhibits retinoblastoma growth in vitro and in vivo.