Fig. 1
Targeting the Arf6-Amap1 pathway by shAmap1 or silvestrol leads to therapeutic synergy with anti-PD-1 ICB. a On day 0, C57BL/6 mice (8 to 10-week old females, CLEA Japan) were injected subcutaneously with 2 × 106 KPC cells, in which Amap1 was silenced by shRNAs (shAmap1 #1 and #2) or that were treated with an irrelevant shRNA (Irr), as described previously [12]. On days 10, 14, and 17, mice were injected intraperitoneally with 3 mg/kg of anti-PD-1 Ab or control IgG according to European Medicines Agency (https://www.ema.europa.eu/en/documents/assessment-report/nivolumab-bms-epar-public-assessment-report_en.pdf). Tumor sizes were measured every 2 to 4 days, starting on day 5. Tumor sizes measured on day 24 are shown in the right panel. Error bars represent the mean ± s.e.m. ****P < 0.0001. b C57BL/6 mice, inoculated subcutaneously with control KPC cells (Irr) or Amap1-silenced KPC cells (shAmap1 #2) as in a, were treated with 3 mg/kg of anti-PD-1 Ab, control IgG, or 0.5 mg/kg of silvestrol, as indicated in the timeline. Tumor sizes measured on day 24 are shown in the right panel. Error bars represent the mean ± s.e.m. ***P < 0.001, ****P < 0.0001. c Western blot demonstrating the suppression of MYC and ARF6 levels by silvestrol in PDAC cells. β-Actin was used as a control