Figure 4.
Combination therapy has superior anti-tumor response on Hepa1-6 tumor model. (A) Hepa1-6 cancer cells were plated at 1.0 × 104/well in a 96-well plate and infected with vvDD-IL15-Rα (MOI = 0, 0.1, 0.5) and/or erastin (0.25, 1.0 µm) the next day. Cell viability was determined at 24 h after treatment using MTS assay. (B–D) B6 mice were inoculated subcutaneously (s.c.) with 2.0 × 106 Hepa1-6 tumor cells in 60 µL volume and randomly divided into required groups (n = 5 in each group). When tumor nodules reached ~5 × 5 mm, vvDD-IL15-Rα were intratumorally (i.t.) injected with 2.0 × 107 pfu/50 µL for only one injection; erastin was intraperitoneally (i.p.) injected daily with 20 mg/kg for seven total injections. (B) The graphs represent a comparison of tumor growth in different treatment groups. (C) The survival of tumor-bearing mice was monitored using Kaplan–Meier analysis and statistical analyses were performed using a log rank test. (D) Tumor formation rate on day 12 post rechallenge s.c. with 2.0 × 106 Hepa1-6 cells. Two-way ANOVA was used to analyze the data (*, p < 0.05; **, p < 0.01; ****, p < 0.0001; and ns: not significant). This experiment was performed once.