Fig. 8: Targeting protein synthesis in basal PDAC.

a WB of puromycin incorporation, PARP, HMGA2, and ACTIN in two basal and two classical cell lines treated with homoharringtonine (HHT). b WB of puromycin incorporation, HMGA2, and ACTIN in KC and K28C cell lines treated with HHT for 24 h. c–d, Representative brightfield color images of crystal violet-staining (c) and relative growth (d) of KC and K28C murine PDA cells treated with increasing doses of HHT for 24 h. Scale bar = 100 µm. Data are displayed as means ± s.e.m (n = 4 biological replicates); asterisks, P values after unpaired, two-tailed t test. **P = 0.0082 K28C-3 vs KC-1, 10 nM HHT; ***P = 0.0003 K28C-3 vs KC-1, 100 nM HHT. e Relative IC50s of two classical PDAC lines engineered to overexpress HMGA2 upon dox-treatment. Cells were treated with increasing doses of HHT. Data are displayed as means± s.e.m (n = 5 biological replicates); asterisks, P values after unpaired, two-tailed t test. ***P = 0.0003 HMGA2 WT vs EMPTY, AsPC-1; ****P < 0.0001 HMGA2 WT vs EMPTY, HPAF-II. f Immunohistochemistry for HMGA2 in one basal (PAAD155) and one classical (PAAD200) PDX model. Scale bar = 100µm g–h, Tumor volume of PAAD155 (g) and PAAD200 (h) xenografts after treatment with twice-daily HHT (0.5 mg/kg, dashed) compared with vehicle control (DPBS, solid) for 21 days. N(DPBS) = 7 mice, n(HHT) = 5 mice for PAAD155 and n(DPBS) = 9 mice, n(HHT) = 9 mice for PAAD200. Data are displayed as means ± s.e.m; P values after paired, two-tailed t test. i–j, Whole-body weights of mice implanted with PAAD155 (i) and PAAD200 ( j ) xenografts after treatment with twice-daily HHT (0.5 mg/kg, dashed) compared with vehicle control (DPBS, solid) for 21 days. N(DPBS) = 7 mice, n(HHT) = 5 mice for PAAD155 and N(DPBS) = 9 mice, n(HHT) = 9 mice for PAAD200. k The PAAD155 cohort in (g) was monitored for survival up to 8 weeks after treatment. Kaplan-Meier analysis and log-rank P values are shown between groups. Source data are provided as a Source Data file.