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

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-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.