Oncolytic Reovirus (pelareorep) Induces Autophagy in KRAS-mutated Colorectal Cancer.

摘要: PURPOSE To explore the effects of pelareorep on autophagy in multiple models colorectal cancer, including patient-derived peripheral blood mononuclear cells (PBMCs). EXPERIMENTAL DESIGN HCT116 [KRAS mutant (mut)] and Hke3 wild-type (WT)] were treated with (multiplicity infection, 5) harvested at 6 9 hours. LC3 A/B expression was determined by immunofluorescence flow cytometry; five autophagic proteins analyzed Western blotting. The 88 genes qRT-PCR. Syngeneic mouse models, CT26/Balb-C (KRAS mut) MC38/C57B6 WT), developed (10 × 106 plaque-forming unit/day) intraperitoneally. Protein RNA extracted from tumor tissues. PBMCs experimental three control patients sampled 0 (pre) 48 hours, days 8 15. gene normalized to "pre" using 2-ΔΔCt method. RESULTS Pelareorep induced significant upregulation as compared (3.24 8.67 ×), cytometry (2.37 2.58 autophagosome formation (2.02 1.57 respectively; all P 4 ×; hours; < 0.05), 12 transcripts CT26 (qRT-PCR), 14 human (P 0.05) observed. A/B, RICTOR, RASD1 upregulated model systems. CONCLUSIONS hijacks host machinery KRAS-mut conditions augment its propagation preferential oncolysis cancer cells.