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Fig. 5 | Journal of Experimental & Clinical Cancer Research

Fig. 5

From: Targeting CRABP-II overcomes pancreatic cancer drug resistance by reversing lipid raft cholesterol accumulation and AKT survival signaling

Fig. 5

SNIPER-11 enhanced the efficacy of gemcitabine in PDAC. (A, B) SNIPER-11 increased gemcitabine induced Panc-1 or GR2000 cell apoptosis. Cells were treated with the combination of SNIPER-11 and gemcitabine for 72 h and cleaved caspase-3/cleaved PARP were detected by western blots. (C, D, E, F) SNIPER-11 treatment reduced raft-cholesterol accumulation and AKT activation. Panc-1 cells (C, D) and GR4000 cells (E, F) were treated with 5 µM SNIPER-11 for 48 h, then the lipid raft cholesterol was assessed using cholesterol assay kit. As to AKT signaling, after 48 h treatment with 5 µM SNIPER-11, the starved cells were stimulated with 100 nM insulin for different time as denotes. (G, H, I) The synergistic effect between SNIPER-11 and gemcitabine in PDX. 1 × 106 PDX single cells were orthotopically injected to pancreas of NSG mice. Mice were grouped and received DMSO, SNIPER-11, gemcitabine or the combination of SNIPER-11 and gemcitabine at 4 weeks after transplantation as described in Materials and Methods. After 3 weeks treatment, tumors were resected and analyzed. Tumor volume = ½ (width x width x length) (H). Tumors were further digested to single cells and lipid raft fraction of these tumor cells were isolated and submitted to cholesterol assays (I). (J, K, L) The synergistic effect between SNIPER-11 and gemcitabine in gemcitabine-resistant CDX. 1 × 106 GR4000 cells were subcutaneously injected to the lower flank of nude mice. Mice were grouped and received DMSO, SNIPER-11, gemcitabine or the combination of SNIPER-11 and gemcitabine at 3 weeks after implantation. After 3 weeks of treatment, tumors were resected (J) and weighed (K). Tumors were combined and digested to single cells. After depletion of tumor-infiltrating immune cells, the lipid raft fraction of enriched tumor cells was isolated and submitted to cholesterol assays (L). The mean comparison between different groups by student t-test. *, p < 0.05; **, p < 0.01

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