MDM2抑制剂RG-7388诱导弥漫性大B淋巴瘤细胞凋亡和周期阻滞  

MDM2 Inhibitor RG-7388 Promotes Apoptosis and Cell Cycle Arrest of Diffuse Large B Cell Lymphoma

作　　者：庄燕 黄豪 周俊邑 潘婷 丁晓蓉 袁颖[3] 仲小敏 ZHUANG Yan;HUANG Hao;ZHOU Junyi;PAN Ting;DING Xiaorong;YUAN Ying;ZHONG Xiaomin(Department of Oncology,The Huai’an Clinical College of Xuzhou Medical University,Huai’an 223300,China;Blood Diseases Institute of Xuzhou Medical University,Xuzhou 221004,China;Department of Oncology,Huai’an First People’s Hospital of Jiangsu Province,Huai’an 223300,China)

机构地区：[1]徐州医科大学淮安临床学院肿瘤内科,淮安223300 [2]徐州医科大学血液病研究所,徐州221004 [3]江苏省淮安市第一人民医院肿瘤内科,淮安223300

出　　处：《肿瘤防治研究》2023年第3期243-248,共6页Cancer Research on Prevention and Treatment

摘　　要：目的探讨MDM2抑制剂RG-7388对弥漫性大B淋巴瘤(DLBCL)细胞增殖、细胞周期和凋亡的影响。方法用2、4和8μmol/L RG7388处理DLBCL细胞株SUDHL2和HBL1,CCK8法和EdU法检测细胞增殖,Annexin V-FITC/PI双染和Caspase 3/7-Glo^(TM)酶活法检测细胞凋亡,流式细胞术检测细胞周期,蛋白质印迹法检测细胞周期和凋亡相关蛋白表达变化。结果RG7388抑制SUDHL2和HBL1细胞的IC50分别为3.36和3.76µmol/L,且RG7388的抑制作用呈剂量依赖性。不同浓度RG7388处理SUDHL2和HBL1细胞,G_(1)期细胞和凋亡细胞比例均显著高于对照组(均P<0.05)。随着RG7388浓度增高,Caspase 3/7酶活性逐渐增加,p53、p27、p21、PARP表达增加,Mcl-1和Bcl-x_(L)表达下调(均P<0.05)。结论MDM2抑制剂RG7388抑制DLBCL细胞增殖,通过p53通路引起G_(1)期细胞阻滞并诱导细胞凋亡。Objective To investigate the effect of MDM2 inhibitor RG-7388 on the proliferation,cell cycle,and apoptosis of diffuse large B-lymphoma(DLBCL)cells.Methods DLBCL cell strains SUDHL2 and HBL1 were treated with 2,4,and 8μmol/LRG7388,respectively.Cell proliferation was detected by CCK8 and EdU methods.Apoptosis was measured by Annexin V–FITC/PI double staining and Caspase 3/7-Glo enzyme activity methods.Cell cycle was assessed by flow cytometry.Changes in the expression of cell cycle and apoptosis-related proteins were determined by Western blot.Results The IC_(50) of RG7388 for inhibiting SUDHL2 and HBL1 cells were 3.36 and 3.76µmol/L,respectively,and the inhibitory effect of RG7388 was dose dependent.The proportions of G_(1) phase and apoptotic cells in the SUDHL2 and HBL1 cells treated with different doses of RG7388 were significantly higher than those in the control group(all P<0.05).The activity of Caspase 3/7 increased gradually with RG7388 concentration,compared with that in the control group.The expression levels of p53,p27,p21,and PARP increased,whereas the expression of Mcl-1 and Bcl-x_(L) was down-regulated(all P<0.05).Conclusion MDM2 inhibitor RG-7388 inhibits the proliferation of DLBCL cells,triggers cell cycle arrest in the G1 phase,and induces apoptosis through the p53 pathway.

关 键 词：弥漫性大B细胞淋巴瘤 MDM2抑制剂 细胞凋亡 细胞周期 

分 类 号：R73-3[医药卫生—肿瘤]