To investigate the effects of daptomycin (DAP) on the proliferation, apoptosis, and cell cycle of U266 [U266B1] human multiple myeloma cells (U266).

U266 cells were divided into the following groups: normal control group (NC group), DAP 20 μM group (DAP20), DAP 40 μM group (DAP40), DAP 80 μM group (DAP80), BZ 50 nM group (BZ50), and DAP 80 μM + BZ 50 nM group (DAP80+BZ50). U266 cells were treated with varying concentrations of DAP (0, 20, 40, and 80 μM), 50 nM bortezomib (BZ), and combination of DAP (80 μM) plus BZ (50 nM). Effects were assessed using cell counting kit-8 (CCK-8) assays, Western blotting (WB), flow cytometry, and quantitative real-time polymerase chain reaction (qPCR).

At 24 h post-treatment: Cell viability rates were recorded as (97.13±2.51)%, (96.80±3.44)%, (85.48±3.28)%, (81.56±2.09)%, (60.78±2.80)%, and (38.09±2.09)% for DAP alone (0-80 μM), BZ monotherapy, and combinatorial treatment, respectively. Early apoptotic cell proportions measured via flow cytometry showed values of (7.50±0.84)%, (8.20±1.41)%, (9.07±1.22)%, (13.14±2.27)%, (14.51±2.58)%, and (15.17±1.87)% across groups. Proportions of cells in G1 phase were determined to be (33.40±1.48)%, (33.03±2.49)%, (31.50±1.40)%, (38.59±1.54)%, (36.94±1.13)%, and (39.43±1.40)%. Relative expression levels of ribosomal protein S19 (RPS19) mRNA exhibited fold changes of 0.99±0.09, 1.00±0.14, 0.66±0.04, 0.61±0.06, 0.55±0.04, and 0.53±0.07, while corresponding protein levels via WB analysis were 1.08±0.05, 0.97±0.03, 0.90±0.02, 0.87±0.04, 0.89±0.04, and 0.57±0.03. Statistically significant differences (all P<0.001) were observed in BZ50, DAP80, and their combination compared to DAP 0 μM group.

DAP may exert its inhibitory effect on U266 cell proliferation and promote apoptosis by downregulating the expression of RPS19. This study provides a potential therapeutic drug for the treatment of multiple myeloma.