Figure 4.
Targeting STAT1 enhances the antilymphoma activity of oncolytic reovirus. (A) Silencing STAT1 expression in TCL cell lines. STAT1 was knocked down in parental Karpas-299 and HuT-78 cells using 3 different lentiviral shRNA constructs, and efficiency was assessed by immunoblotting. STAT1 shRNA #1 was used for all experiments. (B) Reolysin exhibits greater antilymphoma activity in TCL cells with diminished STAT1 levels. TCL cells infected with Control and STAT1 shRNA were treated with the indicated concentrations of Reolysin for 72 hours, and cell viability was determined by MTT assay. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with Control shRNA cells treated with the same concentration of Reolysin. (C) Reovirus viral load is significantly greater in TCL cells with STAT1 knockdown. Karpas-299 and HuT-78 cells were treated for 48 hours with 45 and 90 PFUs Reolysin per cell, respectively. Reovirus accumulation was visualized by electron microscopy. Circles indicate reovirus accumulation. Quantification of reovirus in Control and STAT1 shRNA TCL cells. The number of reovirus particles per cell was quantified using ImageJ software. Data are shown as mean ± SD (n = 5). *P < .05 indicates a significant difference compared with Control shRNA cells treated with Reolysin. (D) Treatment with the JAK inhibitor ruxolitinib sensitizes TCL cells to Reolysin treatment. Parental and belinostat-resistant Karpas-299 and HuT-78 cells were treated with 45 and 90 PFUs Reolysin per cell, respectively, 5 μM ruxolitinib, or the combination for 72 hours, and cell viability was measured by MTT assay. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with Control or **P < .05 for treatment with either ruxolitinib or Reolysin as a single agent.

Targeting STAT1 enhances the antilymphoma activity of oncolytic reovirus. (A) Silencing STAT1 expression in TCL cell lines. STAT1 was knocked down in parental Karpas-299 and HuT-78 cells using 3 different lentiviral shRNA constructs, and efficiency was assessed by immunoblotting. STAT1 shRNA #1 was used for all experiments. (B) Reolysin exhibits greater antilymphoma activity in TCL cells with diminished STAT1 levels. TCL cells infected with Control and STAT1 shRNA were treated with the indicated concentrations of Reolysin for 72 hours, and cell viability was determined by MTT assay. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with Control shRNA cells treated with the same concentration of Reolysin. (C) Reovirus viral load is significantly greater in TCL cells with STAT1 knockdown. Karpas-299 and HuT-78 cells were treated for 48 hours with 45 and 90 PFUs Reolysin per cell, respectively. Reovirus accumulation was visualized by electron microscopy. Circles indicate reovirus accumulation. Quantification of reovirus in Control and STAT1 shRNA TCL cells. The number of reovirus particles per cell was quantified using ImageJ software. Data are shown as mean ± SD (n = 5). *P < .05 indicates a significant difference compared with Control shRNA cells treated with Reolysin. (D) Treatment with the JAK inhibitor ruxolitinib sensitizes TCL cells to Reolysin treatment. Parental and belinostat-resistant Karpas-299 and HuT-78 cells were treated with 45 and 90 PFUs Reolysin per cell, respectively, 5 μM ruxolitinib, or the combination for 72 hours, and cell viability was measured by MTT assay. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with Control or **P < .05 for treatment with either ruxolitinib or Reolysin as a single agent.

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