Induced Apoptosis in Multiple Myeloma Cells Expressing miR-21 Through AKT/FOXO1/BIM Signaling

Multiple myeloma is characterized by clonal proliferation of plasma cells, accounting for 10% of all hematologic cancers. Gambogic acid has shown its efficacy in several hematological malignancies. In this study, we investigated the effect and mechanism for gambogic acid induced apoptosis in multiple myeloma cells with high expression of miR-21. miR-21 inhibitor and negative control inhibitor were transfected into human myeloma U266 cell lines, and expression of miR-21 in U266 cells was detected by quantitative RT-PCR. The effect of gambogic acid with different concentrations on the proliferation of U266 cells was detected by CCK-8 assay, while the effect of gambogic acid on apoptosis was analyzed by Annexin V/PI assay in cells expressing different mRNA levels of miR-21. Results showed that gambogic acid inhibited the proliferation of U266 cells in a concentration and time dependent manner. The U266 cells transfected with miR-21 inhibitor were more sensitive to gambogic acid and apoptotic cells were elevated significantly. Mechanism research revealed that gambogic acid effectively inhibited the phosphorylation of AKT, down-regulated the expression of p-AKT(S308), and increased the expression of FOXO1 and Bim as revealed by Western blot assay. In conclusion, gambogic acid can induce the proliferation and apoptosis of U266 cells with higher expression of miR-21 through mediation of AKT/FOXO1/BIM signaling.