Application of USP7 inhibitors to promote apoptosis in temozolomide-resistant primary glioblastoma cells

PAN Tingzheng; WANG Jianwei; CHEN Kaiyuan; WANG Zhengwei; LI Qingzhong; SONG Zhao; LIU Jiangang

Abstract：Objective To study the effect of applying P5091,an inhibitor of USP7,on TMZ-resistant primary glioblastoma.Methods The expression of USP7 in different primary glioblastoma tissues and recurrent glioblastoma was analyzed by immunohistochemistry.Differences in USP7 expression in primary glioblastoma tissues and recurrent glioblastoma tissues were detected by Western Blot.Differences in USP7 expression in primary glioblastoma cells SHG-140 and its TMZ-resistant strain SHG-140R were detected by Western Blot.The effect of P5091 on the survival of SHG-140 and SHG-140R was detected by CCK8.The effect of P5091 on SHG-140 and SHG-140R apoptosis was detected by flow cytometry.The expression of apoptotic proteins in SHG-140R after P5091 treatment was detected by Western Blot.Results The expression of USP7 in glioblastoma was higher than that in normal brain tissues(P＜0.0 1),and the difference of USP7 expression was not obvious in different primary glioblastoma tissues and recurrent glioblastoma.Compared with SHG-140,the survival rate of SHG-140R decreased more significantly after the application of P5091,and the flow cytometry results suggested that the apoptosis of SHG-140R cells was more significant after the application of P5091(P＜0.01).Western Blot results showed that the apoptotic proteins CLEAVED-PARP,CLEAVED-CASPASE9,and CLEAVED-CASPASE3 expression were significantly elevated in SHG-140R cells(P＜0.05,P＜0.01).Conclusion P5091 can promote apoptosis in TMZ-resistant primary glioblastoma cells.