Fig. 4: Effective doxorubicin treatment decreases urinary diacetylspermine in sensitive TNBC-PDX with high baseline SAT1 function.

a Tumor growth curves showing TM89 resistance and TM99 sensitivity after treatment with vehicle (5% dextrose, IV) or doxorubicin (DOXO, 2 mg/kg, IV), mean ± s.e.m., n = 6. b Quantified urinary diacetylspermine and c correlation with tumor volume. d Plasma diacetylspermine and tumor urea cycle (e), polyamine (f) and acetylated polyamine (g) metabolites from TM89 and TM99 TNBC-PDX mice, n = 6. h Doxorubicin dose-response in TM99 and TM98 ex vivo TNBC-PDX tissue slices, n = 3. Urea cycle (i), polyamine (j) and acetylated polyamine (k) metabolites demonstrating elevated spermine and spermine acetylation in TM99 compared to TM89 ex vivo tissue slices, independent of doxorubicin (1 µM) treatment. Stable isotope metabolic flux in TM89 and TM99 ex vivo tissue slices treated with ¹³C-glucose (l), ¹⁵N-methionine (m), and ¹⁵N-arginine (n), vehicle (DMSO) or 1 µM doxorubicin for 24 h. Ex vivo slice experiments were performed in triplicate, n = 6. All data are presented as mean ± s.e.m. Significance was determined by two-sided one-way ANOVA with Tukey’s test or two-way repeated measures ANOVA with Sidak’s correction, *P < 0.05, **P < 0.01, ***P < 0.01, ****P < 0.0001; ^#P < 0.05, ^####P < 0.0001 vs TM99 control.