Fig 1: Inhibiting glycine utilization via SLC6A9 knockdown or betaine treatment reduces proliferation and enhances the effect of BTZ on MM cells.a SLC6A5 and SLC6A9 expression in ARP1 treated with BTZ. b Glycine concentrations in ARP1 Scr, ARP1 SLC6A9sh1, and ARP1 SLC6A9sh2 cells. c GSH levels in ARP1 Scr, ARP1 SLC6A9sh1, and ARP1 SLC6A9sh2 cells. d Clonogenic analysis of ARP1 Scr, ARP1 SLC6A9sh1, and ARP1 SLC6A9sh2 cells with or without BTZ treatment. e CCK-8 assay of ARP1 Scr, ARP1 SLC6A9sh1, and ARP1 SLC6A9sh2 cells treated with different doses of BTZ. f The chemical structures of glycine, N,N-Dimethylglycine, and betaine. g Cell viability of ARP1 and 5TGM1 treated with N,N-Dimethylglycine or betaine. h Glycine levels in ARP1 and 5TGM1 cells with or without betaine treatment. i GSH levels in ARP1 and 5TGM1 with or without betaine treatment. j Live imaging luminescence intensity in 5TGM1 MM mice treated with physiological saline, BTZ (1 mg/kg), or betaine (500 mg/kg) (n = 5 for each group). k Quantification of tumor-associated luminescence intensity in 5TGM1 MM mice at 2 (n = 5 in each group), 4 (n = 5 in each group), and 6 (n = 4 in control group, n = 5 in other groups) weeks. l IgG2b concentrations in 5TGM1 MM mice treated with physiological saline, BTZ, or betaine. m The survival curves of 5TGM1 MM mice (Log-rank test). n The combination index of betaine and BTZ treatment in ARP1 was analyzed by the Chou–Talalay method. o The ROS levels in ARP1 cells with or without BTZ and betaine treatment. p CCK-8 assays of ARP1 treated with different doses of BTZ and with or without betaine and GSH. q Western blotting of cleaved caspase3, PARP, ?-H2AX, and ß-actin in ARP1 and 5TGM1 with or without BTZ, betaine and GSH. n = 3 independent experiments; Results represent means ± SD in (a–e, g–i, o, p). Unpaired two-sided t-test was used in (a–c, e, h, i, k, o, p); paired two-sided t-test was used in was applied in (l). Source data are provided as a Source Data file.