Fig. 2: Pharmacological inhibition of PIKfyve blocks pancreatic cancer progression in vivo.
From: Targeting PIKfyve-driven lipid metabolism in pancreatic cancer
a, Immunoblot analysis demonstrating stabilization of PIKfyve by apilimod (1,000 nM) or ESK981 (1,000 nM) in a cellular thermal shift assay in 7940B cells. b,c, Relative abundance of PtdIns(3,5)P2 (b) and PtdIns5P (c) in PANC1 cells following treatment with apilimod (1,000 nM) or ESK981 (1,000 nM) for the time indicated. Bars show ±s.d. d, Schematic of a prophylactic efficacy study of ESK981 on KPC mice. Mouse cartoon adapted from Adobe Stock Image (asset no. 304271210). e, Pancreatic tissue weight in vehicle or ESK981-treated KPC mice in comparison with age-matched wild-type (WT) mice. Boxes represent the 25th and 75th percentiles; whiskers represent the range (one-way ANOVA with Dunnett’s test). f, Quantification of lesions (PanIN or PDAC) in samples from e. Boxes represent the 25th and 75th percentiles; whiskers represent the range (unpaired two-tailed t-test). g, End-point pancreas + tumour weight normalized to total body weight of mice with 7940B orthotopic tumours. Pancreata of six age-matched non-tumour-bearing C57BL/6 mice were used as references. Boxes represent 25th and 75th percentiles; whiskers represent the range (one-way ANOVA with Tukey’s test). h, Representative H&E (top) and CK19 (bottom) images of pancreatic and pancreatic tumour tissues from g. i. Quantification of lesions from the 7940B orthotopic samples in g. Boxes represent 25th and 75th percentiles; whiskers represent the range (unpaired two-tailed t-tests). j, End-point pancreas + tumour weight normalized to total body weight of CB17 SCID mice with UM19 orthotopic tumours. Pancreata of five age-matched non-tumour-bearing CB17 SCID mice were used as references. Boxes represent 25th and 75th percentiles; whiskers represent the range (one-way ANOVA with Tukey’s test). k, Representative histology images showing CK19 IHC and H&E staining of the samples from j. Scale bars: h, 200 μm (top, main images), 5 μm (top insets), 5 mm (bottom); k, 5 mm (left), 200 μm (middle and right, main images), 50 μm (insets).
