Fig. 8: Targeting HuR enhances bortezomib-mediated anti-MM effects in vitro and in vivo.

a Treatment of NCI-H929 and OPM2 cells with combinations of CMLD-2 and BTZ for 48 h at the indicated concentrations had synergistic effects on cell proliferation. b, c After HuR-knockdown NCI-H929 and OPM2 cells were treated with bortezomib (BTZ, 1 nM or 4 nM) for 48 h, cell viability was measured with CCK-8 assays. Following the treatment of HuR-overexpressing NCI-H929 and OPM2 cells with BTZ (4 nM or 6 nM) for 48 h, cell viability was determined with CCK-8 assays. d NCI-H929 and OPM2 cell lines were treated with BTZ (3 nM), CMLD-2 (15 μM), or a combination for 24 h. The early and late apoptosis rates were analyzed by Annexin V/PI double staining. e, f NCI-H929 cells were inoculated subcutaneously into the flanks of NOG mice (3 × 10⁶ cells per mouse). After the subcutaneous tumors were measured (d1), the above mice were randomly divided into four groups (n = 5 per group). Tumor volume was measured and recorded for NCI-H929 xenograft mice treated with vehicle, CMLD-2 (20 mg/kg, once every other day, intraperitoneally), BTZ (1 mg/kg, d 1, d 4, d 8, and d 11, intravenously), or CMLD-2 + BTZ. g These subcutaneous tumors were dissected from mice in each group and photographed at the end of the experiment (d 14). h Subcutaneous tumors from the above groups of mice were measured, weighed, and compared. The data are shown as the means ± SD and were analyzed by Student’s t-test (b, c) or one-way ANOVA (d, f, h). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.