MDM2 Inhibitor RG-7388 Promotes Apoptosis and Cell Cycle Arrest of Diffuse Large B Cell Lymphoma / 肿瘤防治研究

ABSTRACT

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 8 μmol/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 IC50 of RG7388 for inhibiting SUDHL2 and HBL1 cells were 3.36 and 3.76 μmol/L, respectively, and the inhibitory effect of RG7388 was dose dependent. The proportions of G1 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-xL 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.